CycB/CCNB1 Cancer Research Results

CycB/CCNB1, Cyclin B: Click to Expand ⟱
Source:
Type:
When cyclin B levels are elevated, cells can enter M phase prematurely and strict control over cell division is lost, which is favorable for cancer development.
Cyclin B is a regulatory protein that plays a crucial role in cell cycle progression, particularly in the transition from the G2 phase to mitosis. Its expression levels can significantly impact cancer progression and patient prognosis.
Cyclin B expression is often elevated in various cancers and is generally associated with poor prognosis.
Cyclin B levels:
-Accumulate during S and G2
-Peak at mitotic entry
-Are rapidly destroyed at metaphase–anaphase transition via the APC/C ubiquitin ligase


Scientific Papers found: Click to Expand⟱
2660- AL,    Allicin: A review of its important pharmacological activities
- Review, AD, NA - Review, Var, NA - Review, Park, NA - Review, Stroke, NA
*Inflam↓, It showed neuroprotective effects, exhibited anti-inflammatory properties, demonstrated anticancer activity, acted as an antioxidant, provided cardioprotection, exerted antidiabetic effects, and offered hepatoprotection.
AntiCan↑,
*antiOx↑,
*cardioP↑, This vasodilatory effect helps protect against cardiovascular diseases by reducing the risk of hypertension and atherosclerosis.
*hepatoP↑,
*BBB↑, This allows allicin to easily traverse phospholipid bilayers and the blood-brain barrier
*Half-Life↝, biological half-life of allicin is estimated to be approximately one year at 4°C. However, it should be noted that its half-life may differ when it is dissolved in different solvents, such as vegetable oil
*H2S↑, allicin undergoes metabolism in the body, leading to the release of hydrogen sulfide (H2S)
*BP↓, H2S acts as a vasodilator, meaning it relaxes and widens blood vessels, promoting blood flow and reducing blood pressure.
*neuroP↑, It acts as a neuromodulator, regulating synaptic transmission and neuronal excitability.
*cognitive↑, Studies have suggested that H2S may enhance cognitive function and protect against neurodegenerative diseases like Alzheimer's and Parkinson's by promoting neuronal survival and reducing oxidative stress.
*neuroP↑, various research studies suggest that the neuroprotective mechanisms of allicin can be attributed to its antioxidant and anti-inflammatory properties
*ROS↓,
*GutMicro↑, may contribute to the overall health of the gut microbiota.
*LDH↓, Liu et al. found that allicin treatment led to a significant decrease in the release of lactate dehydrogenase (LDH),
*ROS↓, allicin's capacity to lower the production of reactive oxygen species (ROS), decrease lipid peroxidation, and maintain the activities of antioxidant enzymes
*lipid-P↓,
*antiOx↑,
*other↑, allicin was found to enhance the expression of sphingosine kinases 2 (Sphk2), which is considered a neuroprotective mechanism in ischemic stroke
*PI3K↓, allicin downregulated the PI3K/Akt/nuclear factor-kappa B (NF-κB) pathway, inhibiting the overproduction of NO, iNOS, prostaglandin E2, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha induced by interleukin-1 (IL-1)
*Akt↓,
*NF-kB↓,
*NO↓,
*iNOS↓,
*PGE2↓,
*COX2↓,
*IL6↓,
*TNF-α↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
*MPO↓, Furthermore, allicin significantly decreased tumor necrosis factor-alpha (TNF-α) levels and myeloperoxidase (MPO) activity, indicating its neuroprotective effect against brain ischemia via an anti-inflammatory pathway
*eff↑, Allicin, in combination with melatonin, demonstrated a marked reduction in the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), Kelch-like ECH-associated protein 1 (Keap-1), and NF-κB genes in rats with brain damage induced by acryl
*NRF2↑, Allicin treatment decreased oxidative stress by upregulating Nrf2 protein and downregulating Keap-1 expression.
*Keap1↓,
*TBARS↓, It significantly reduced myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS) levels,
*creat↓, and decreased blood urea nitrogen (BUN), creatinine, LDH, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels.
*LDH↓,
*AST↓,
*ALAT↓,
*MDA↓,
*SOD↑, Allicin also increased the activity of superoxide dismutase (SOD) as well as the levels of glutathione S-transferase (GST) and glutathione (GSH) in the liver, kidneys, and brain
*GSH↑,
*GSTs↑,
*memory↑, Allicin has demonstrated its ability to improve learning and memory deficits caused by lead acetate injury by promoting hippocampal astrocyte differentiation.
chemoP↑, Allicin safeguards mitochondria from damage, prevents the release of cytochrome c, and decreases the expression of pro-apoptotic factors (Bax, cleaved caspase-9, cleaved caspase-3, and p53) typically activated by cisplatin
IL8↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
Cyt‑c↑, In addition, allicin was reported to induce cytochrome c, increase expression of caspase 3 [86], caspase 8, 9 [82,87], caspase 12 [80] along with enhanced p38 protein expression levels [81], Fas expression levels [82].
Casp3↑,
Casp8↑,
Casp9↑,
Casp12↑,
p38↑,
Fas↑,
P53↑, Also, significantly increased p53, p21, and CHK1 expression levels decreased cyclin B after allicin treatment.
P21↑,
CHK1↓,
CycB/CCNB1↓,
GSH↓, Depletion of GSH and alterations in intracellular redox status have been found to trigger activation of the mitochondrial apoptotic pathway was the antiproliferative function of allicin
ROS↑, Hepatocellular carcinoma (HCC) cells were sensitised by allicin to the mitochondrial ROS-mediated apoptosis induced by 5-fluorouracil
TumCCA↑, According to research findings, allicin has been shown to decrease the percentage of cells in the G0/G1 and S phases [87], while causing cell cycle arrest at the G2/M phase
Hif1a↓, Allicin treatment was found to effectively reduce HIF-1α protein levels, leading to decreased expression of Bcl-2 and VEGF, and suppressing the colony formation capacity and cell migration rate of cancer cells
Bcl-2↓,
VEGF↓,
TumCMig↓,
STAT3↓, antitumor properties of allicin have been attributed to various mechanisms, including promotion of apoptosis, inhibition of STAT3 signaling
VEGFR2↓, suppression of VEGFR2 and FAK phosphorylation
p‑FAK↓,

251- AL,    Inhibition of allicin in Eca109 and EC9706 cells via G2/M phase arrest and mitochondrial apoptosis pathway
- in-vitro, ESCC, Eca109 - in-vitro, ESCC, EC9706 - in-vivo, NA, NA
Apoptosis↑,
P53↑,
P21↑,
CHK1↑,
CycB/CCNB1↓,
BAX↑,
Casp3↑,
Casp9↑,
Cyt‑c↑, allicin treatment resulted in Cyt c release from the mitochondria to the cytosol.

1353- And,    Andrographolide Induces Apoptosis and Cell Cycle Arrest through Inhibition of Aberrant Hedgehog Signaling Pathway in Colon Cancer Cells
- in-vitro, Colon, HCT116
ChemoSen↑, combination with 5FU, andrographolide exhibited synergistic effect
TumCCA↑, G2/M phase arrest
CDK1↓,
CycB/CCNB1↓,
HH↓, repressed the colon cancer cell growth via inhibiting Hh signaling pathway
Smo↓,
Gli1↓,

1545- Api,    The Potential Role of Apigenin in Cancer Prevention and Treatment
- Review, NA, NA
TNF-α↓, Apigenin downregulates the TNFα
IL6↓,
IL1α↓,
P53↑,
Bcl-xL↓,
Bcl-2↓,
BAX↑,
Hif1a↓, Apigenin inhibited HIF-1alpha and vascular endothelial growth factor expression
VEGF↓,
TumCCA↑, Apigenin exposure induces G2/M phase cell cycle arrest, DNA damage, apoptosis and p53 accumulation
DNAdam↑,
Apoptosis↑,
CycB/CCNB1↓,
cycA1/CCNA1↓,
CDK1↓,
PI3K↓,
Akt↓,
mTOR↓,
IKKα↓, , decreases IKKα kinase activity,
ERK↓,
p‑Akt↓,
p‑P70S6K↓,
p‑S6↓,
p‑ERK↓, decreased the expression of phosphorylated (p)-ERK1/2 proteins, p-AKT and p-mTOR
p‑P90RSK↑,
STAT3↓,
MMP2↓, Apigenin down-regulated Signal transducer and activator of transcription 3target genes MMP-2, MMP-9 and vascular endothelial growth factor
MMP9↓,
TumCP↓, Apigenin significantly suppressed colorectal cancer cell proliferation, migration, invasion and organoid growth through inhibiting the Wnt/β-catenin signaling
TumCMig↓,
TumCI↓,
Wnt/(β-catenin)↓,

177- Api,    Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression
- in-vitro, BC, MDA-MB-231
Cyc↓, Cyclin A
CycB/CCNB1↓,
CDK1↓,
P21↑,
PCNA↝,
HDAC↓, apigenin treatment for 48 h suppressed HDAC activity in MDA-MB-231 cells in a dose-dependent manner
TumCP↓, Apigenin Inhibited MDA-MB-231 Cell Proliferation
TumCCA↑, Apigenin Induced G2/M Arrest in MDA-MB-231 Cells
ac‑H3↑, H3 acetylation increased in time-dependent
TumW↓, apigenin treatment significantly reduced the tumor volume and tumor weight
TumVol↓,

173- Api,    Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells
- in-vitro, Colon, HCT116
CycB/CCNB1↓,
cDC2↓,
CDC25↓,
P53↑,
P21↑,
cl‑PARP↑, cleavage
proCasp8↓, Apigenin induced poly (ADP-ribose) polymerase (PARP) cleavage and decreased the levels of procaspase-8, -9 and -3
proCasp9↓,
proCasp3↓,

3391- ART/DHA,    Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug
- Review, Var, NA
TumCP↓, inhibiting cancer proliferation, metastasis, and angiogenesis.
TumMeta↓,
angioG↓,
TumVol↓, reduces tumor volume and progression
BioAv↓, artemisinin has low solubility in water or oil, poor bioavailability, and a short half-life in vivo (~2.5 h)
Half-Life↓,
BioAv↑, semisynthetic derivatives of artemisinin such as artesunate, arteeter, artemether, and artemisone have been effectively used as antimalarials with good clinical efficacy and tolerability
eff↑, preloading of cancer cells with iron or iron-saturated holotransferrin (diferric transferrin) triggers artemisinin cytotoxicity
eff↓, Similarly, treatment with desferroxamine (DFO), an iron chelator, renders compounds inactive
ROS↑, ROS generation may contribute with the selective action of artemisinin on cancer cells.
selectivity↑, Tumor cells have enhanced vulnerability to ROS damage as they exhibit lower expression of antioxidant enzymes such as superoxide dismutase, catalase, and gluthatione peroxidase compared to that of normal cells
TumCCA↑, G2/M, decreased survivin
survivin↓,
BAX↑, Increased Bax, activation of caspase 3,8,9 Decreased Bc12, Cdc25B, cyclin B1, NF-κB
Casp3↓,
Casp8↑,
Casp9↑,
CDC25↓,
CycB/CCNB1↓,
NF-kB↓,
cycD1/CCND1↓, decreased cyclin D, E, CDK2-4, E2F1 Increased Cip 1/p21, Kip 1/p27
cycE/CCNE↓,
E2Fs↓,
P21↑,
p27↑,
ADP:ATP↑, Increased poly ADP-ribose polymerase Decreased MDM2
MDM2↓,
VEGF↓, Decreased VEGF
IL8↓, Decreased NF-κB DNA binding [74, 76] IL-8, COX2, MMP9
COX2↓,
MMP9↓,
ER Stress↓, ER stress, degradation of c-MYC
cMyc↓,
GRP78/BiP↑, Increased GRP78
DNAdam↑, DNA damage
AP-1↓, Decreased NF-κB, AP-1, Decreased activation of MMP2, MMP9, Decreased PKC α/Raf/ERK and JNK
MMP2↓,
PKCδ↓,
Raf↓,
ERK↓,
JNK↓,
PCNA↓, G2, decreased PCNA, cyclin B1, D1, E1 [82] CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF
CDK2↓,
CDK4↓,
TOP2↓, Inhibition of topoisomerase II a
uPA↓, Decreased MMP2, transactivation of AP-1 [56, 88] NF-κB uPA promoter [88] MMP7
MMP7↓,
TIMP2↑, Increased TIMP2, Cdc42, E cadherin
Cdc42↑,
E-cadherin↑,

3160- Ash,    Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal
- Review, Var, NA
TumCCA↑, withaferin A suppressed cell proliferation in prostate, ovarian, breast, gastric, leukemic, and melanoma cancer cells and osteosarcomas by stimulating the inhibition of the cell cycle at several stages, including G0/G1 [86], G2, and M phase
H3↑, via the upregulation of phosphorylated Aurora B, H3, p21, and Wee-1, and the downregulation of A2, B1, and E2 cyclins, Cdc2 (Tyr15), phosphorylated Chk1, and Chk2 in DU-145 and PC-3 prostate cancer cells.
P21↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDC2↓,
CHK1↓,
Chk2↓,
p38↑, nitiated cell death in the leukemia cells by increasing the expression of p38 mitogen-activated protein kinases (MAPK)
MAPK↑,
E6↓, educed the expression of human papillomavirus E6/E7 oncogenes in cervical cancer cells
E7↓,
P53↑, restored the p53 pathway causing the apoptosis of cervical cancer cells.
Akt↓, oral dose of 3–5 mg/kg withaferin A attenuated the activation of Akt and stimulated Forkhead Box-O3a (FOXO3a)-mediated prostate apoptotic response-4 (Par-4) activation,
FOXO3↑,
ROS↑, the generation of reactive oxygen species, histone H2AX phosphorylation, and mitochondrial membrane depolarization, indicating that withaferin A can cause the oxidative stress-mediated killing of oral cancer cells [
γH2AX↑,
MMP↓,
mitResp↓, withaferin A inhibited the expansion of MCF-7 and MDA-MB-231 human breast cancer cells by ROS production, owing to mitochondrial respiration inhibition
eff↑, combination treatment of withaferin A and hyperthermia induced the death of HeLa cells via a decrease in the mitochondrial transmembrane potential and the downregulation of the antiapoptotic protein myeloid-cell leukemia 1 (MCL-1)
TumCD↑,
Mcl-1↓,
ER Stress↑, . Withaferin A also attenuated the development of glioblastoma multiforme (GBM), both in vitro and in vivo, by inducing endoplasmic reticulum stress via activating the transcription factor 4-ATF3-C/EBP homologous protein (ATF4-ATF3-CHOP)
ATF4↑,
ATF3↑,
CHOP↑,
NOTCH↓, modulating the Notch-1 signaling pathway and the downregulation of Akt/NF-κB/Bcl-2 . withaferin A inhibited the Notch signaling pathway
NF-kB↓,
Bcl-2↓,
STAT3↓, Withaferin A also constitutively inhibited interleukin-6-induced phosphorylation of STAT3,
CDK1↓, lowering the levels of cyclin-dependent Cdk1, Cdc25C, and Cdc25B proteins,
β-catenin/ZEB1↓, downregulation of p-Akt expression, β-catenin, N-cadherin and epithelial to the mesenchymal transition (EMT) markers
N-cadherin↓,
EMT↓,
Cyt‑c↑, depolarization and production of ROS, which led to the release of cytochrome c into the cytosol,
eff↑, combinatorial effect of withaferin A and sulforaphane was also observed in MDA-MB-231 and MCF-7 breast cancer cells, with a dramatic reduction of the expression of the antiapoptotic protein Bcl-2 and an increase in the pro-apoptotic Bax level, thus p
CDK4↓, downregulates the levels of cyclin D1, CDK4, and pRB, and upregulates the levels of E2F mRNA and tumor suppressor p21, independently of p53
p‑RB1↓,
PARP↑, upregulation of Bax and cytochrome c, downregulation of Bcl-2, and activation of PARP, caspase-3, and caspase-9 cleavage
cl‑Casp3↑,
cl‑Casp9↑,
NRF2↑, withaferin A binding with Keap1 causes an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, which in turn, regulates the expression of antioxidant proteins that can protect the cells from oxidative stress.
ER-α36↓, Decreased ER-α
LDHA↓, inhibited growth, LDHA activity, and apoptotic induction
lipid-P↑, induction of oxidative stress, increased lipid peroxidation,
AP-1↓, anti-inflammatory qualities of withaferin A are specifically attributed to its inhibition of pro-inflammatory molecules, α-2 macroglobulin, NF-κB, activator protein 1 (AP-1), and cyclooxygenase-2 (COX-2) inhibition,
COX2↓,
RenoP↑, showing strong evidence of the renoprotective potential of withaferin A due to its anti-inflammatory activity
PDGFR-BB↓, attenuating the BB-(PDGF-BB) platelet growth factor
SIRT3↑, by increasing the sirtuin3 (SIRT3) expression
MMP2↓, withaferin A inhibits matrix metalloproteinase-2 (MMP-2) and MMP-9,
MMP9↓,
NADPH↑, but also provokes mRNA stimulation for a set of antioxidant genes, such as NADPH quinone dehydrogenase 1 (NQO1), glutathione-disulfide reductase (GSR), Nrf2, heme oxygenase 1 (HMOX1),
NQO1↑,
GSR↑,
HO-1↑,
*SOD2↑, cardiac ischemia-reperfusion injury model. Withaferin A triggered the upregulation of superoxide dismutase SOD2, SOD3, and peroxiredoxin 1(Prdx-1).
*Prx↑,
*Casp3?, and ameliorated cardiomyocyte caspase-3 activity
eff↑, combination with doxorubicin (DOX), is also responsible for the excessive generation of ROS
Snail↓, inhibition of EMT markers, such as Snail, Slug, β-catenin, and vimentin.
Slug↓,
Vim↓,
CSCs↓, highly effective in eliminating cancer stem cells (CSC) that expressed cell surface markers, such as CD24, CD34, CD44, CD117, and Oct4 while downregulating Notch1, Hes1, and Hey1 genes;
HEY1↓,
MMPs↓, downregulate the expression of MMPs and VEGF, as well as reduce vimentin, N-cadherin cytoskeleton proteins,
VEGF↓,
uPA↓, and protease u-PA involved in the cancer cell metastasis
*toxicity↓, A was orally administered to Wistar rats at a dose of 2000 mg/kg/day and had no adverse effects on the animals
CDK2↓, downregulated the activation of Bcl-2, CDK2, and cyclin D1
CDK4↓, Another study also demonstrated the inhibition of Hsp90 by withaferin A in a pancreatic cancer cell line through the degradation of Akt, cyclin-dependent kinase 4 Cdk4,
HSP90↓,

4823- ASTX,    Astaxanthin increases radiosensitivity in esophageal squamous cell carcinoma through inducing apoptosis and G2/M arrest
- in-vitro, ESCC, NA
RadioS↑, It was shown that ATX improved radiosensitivity of ESCC cells and induced apoptosis and G2/M arrest via inhibiting Bcl2, CyclinB1, Cdc2, and promoting Bax expression.
Apoptosis↑,
TumCCA↑,
Bcl-2↓,
CycB/CCNB1↓,
CDC2↓,
BAX↑,

5362- AV,    Anti-cancer effects of aloe-emodin: a systematic review
- Review, Var, NA
AntiCan↑, Aloe-emodin possesses multiple anti-proliferative and anti-carcinogenic properties in a host of human cancer cell lines, with often multiple vital pathways affected by the same molecule.
eff↝, The effects of aloe-emodin are not ubiquitous across all cell lines but depend on cell type.
TumCP↓, most notable effects include inhibition of cell proliferation, migration, and invasion; cycle arrest; induction of cell death;
TumCMig↓,
TumCI↓,
TumCCA↑,
TumCD↑,
MMP↓, mitochondrial membrane and redox perturbations; and modulation of immune signaling.
ROS↑, which coincide with deleterious effects on mitochondrial membrane permea-bility and/or oxidative stress via exacerbated ROS production.
Apoptosis↑, In bladder cancer cells (T24), aloe-emodin induced time-and dose-dependent apoptosis [7]
CDK1↓, reduced levels of cyclin-dependent kinase (CDK) 1, cyclin B1, and BCL-2 after treatment with aloe-emodin.
CycB/CCNB1↓,
Bcl-2↓,
PCNA↓, Increases in cyclin B1, CDK1, and alkaline phosphatase (ALP) activity were observed along with inhibition of proliferating cell nuclear antigen (PCNA), showing decreased proliferation.
ATP↓, human lung non-small cell car¬cinoma (H460). They found a time- de¬pendent reduction in ATP, lower ATP synthase expression
ER Stress↑, hypothesized to cause apoptosis by augmenting endoplasmic reticulum stress [16].
cl‑Casp3↑, (HepG2) cells underwent apoptosis through a cas-pase-dependent pathway with cleavage and activation of caspases-3/9 and cleavage of PARP [24]
cl‑Casp9↑,
cl‑PARP↑,
MMP2↓, Matrix metalloproteinase-2 was significantly decreased, with an increase in ROS and cytosolic calcium.
Ca+2↑,
DNAdam↑, U87 malignant glioma cells through disruption of mitochondrial membrane potential, cell cycle arrest in the S phase, and DNA fragmentation in a time-dependent manner with minimal necrosis
Akt↓, Prostate cancer. Following treatment with aloe-emodin, mTORC2's down¬stream enzymes, AKT and PKCa, were inhibited
PKCδ↓,
mTORC2↓, Proliferation of PC3 cells was inhibited as a result of aloe-emodin binding to mTORC2, with inhibition of mTORC2 kinase activity.
GSH↓, Skin cancer. Intracellular ROS increased, while intra-cellular-reduced glutathione (GSH) was depleted and BCL-2 (anti-apoptotic protein) was down-regulated.
ChemoSen↑, Aloe-emodin also sensitizes skin cancer cells to chemo-therapy. aloe-emodin and emodin potentiated the therapeutic effects of cisplatin, doxo-rubicin, 5-fluorouracil

5498- Ba,    Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis
- in-vitro, Lung, H460
12LOX↓, Baicalein is known as a 12-lipoxygenase (12-LOX) inhibitor.
Dose↝, exposure to 50muM baicalein, cell cycle analysis revealed an increase in the cell population in S-phase.
TumCCA↑,
CDK1↓, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study.
CycB/CCNB1↓,
Apoptosis↑, baicalein induced the most of H460 cell apoptosis after treatment for 48h
Bcl-2↓, accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels.
P53↑,
BAX↑,
TumCP↓, baicalein, a 12-LOX inhibitor, inhibits the proliferation of H460 cells via S-phase arrest and induces apoptosis in association with the regulation of molecules in the cell cycle and apoptosis-related proteins.

2290- Ba,    Research Progress of Scutellaria baicalensis in the Treatment of Gastrointestinal Cancer
- Review, GI, NA
p‑mTOR↓, Baicalein treatment decreased the expression levels of p-mTOR, p-Akt, p-IκB and NF-κB proteins, and suppressed GC cells by inhibiting the PI3K/Akt
p‑Akt↓,
p‑IKKα↓,
NF-kB↓,
PI3K↓,
Akt↓,
ROCK1↓, Baicalin reduces HCC proliferation and metastasis by inhibiting the ROCK1/GSK-3β/β-catenin signaling pathway
GSK‐3β↓,
CycB/CCNB1↓, Baicalein induces S-phase arrest in gallbladder cancer cells by down-regulating Cyclin B1 and Cyclin D1 in gallbladder cancer BGC-SD and SGC996 cells while up-regulating Cyclin A
cycD1/CCND1↓,
cycA1/CCNA1↑,
CDK4↓, Following baicalein treatment, there is a down-regulation of Ezrin, CyclinD1, and CDK4, as well as an up-regulation of p53 and p21 protein levels, thereby leading to the induction of CRC HCT116 cell cycle arrest
P53↑,
P21↑,
TumCCA↑,
MMP2↓, baicalein was able to inhibit the metastasis of gallbladder cancer cells by down-regulating ZFX, MMP-2 and MMP-9.
MMP9↓,
EMT↓, Baicalein treatment effectively inhibits the snail-induced EMT process in CRC HT29 and DLD1 cells
Hif1a↓, Baicalein inhibits VEGF by downregulating HIF-1α, a crucial regulator of angiogenesis
Shh↓, baicalein inhibits the metastasis of PC by impeding the Shh pathway
PD-L1↓, Baicalin and baicalein down-regulate PD-L1 expression induced by IFN-γ by reducing STAT3 activity
STAT3↓,
IL1β↓, baicalein therapy significantly diminishes the levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β), IL-2, IL-6, and GM-CSF
IL2↓,
IL6↓,
PKM2↓, Baicalein, by reducing the expression levels of HIF-1A and PKM2, can inhibit the glycolysis process in ESCC cells
HDAC10↓, Baicalein treatment increases the level of miR-3178 and decreases HDAC10 expression, resulting in the inactivation of the AKT signaling pathways.
P-gp↓, baicalein reverses P-glycoprotein (P-gp)-mediated resistance in multidrug-resistant HCC (Bel7402/5-FU) cells by reducing the levels of P-gp and Bcl-xl
Bcl-xL↓,
eff↓, Baicalein combined with gemcitabine/docetaxel promotes apoptosis of PC cells by activating the caspase-3/PARP signaling pathway
BioAv↓, baicalein suffers from low water solubility and susceptibility to degradation by the digestive system
BioAv↑, Encapsulation of baicalein into liposomal bilayers exhibits a therapeutic efficacy close to 90% for PDAC

2674- BBR,    Berberine: A novel therapeutic strategy for cancer
- Review, Var, NA - Review, IBD, NA
Inflam↓, anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide.
AntiCan↑, elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.
Apoptosis↑,
TumAuto↑,
TumCCA↑,
TumMeta↓,
TumCI↓,
eff↑, BBR is shown to have beneficial effects on cancer immunotherapy.
eff↑, BBR inhibited the release of Interleukin 1 beta (IL-1β), Interferon gamma (IFN-γ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) from LPS stimulated lymphocytes by acting as a dopamine receptor antagonist
CD4+↓, BBR inhibited the proliferation of CD4+ T cells and down-regulated TNF-α and IL-1 and thus, improved autoimmune neuropathy.
TNF-α↓,
IL1↓,
BioAv↓, On the other hand, P-Glycoprotein (P-gp), a secretive pump located in the epithelial cell membrane, restricts the oral bioavailability of a variety of medications, such as BBR. The use of P-gp inhibitors is a common and effective way to prevent this
BioAv↓, Regardless of its low bioavailability, BBR has shown great therapeutic efficacy in the treatment of a number of diseases.
other↓, BBR has been also used as an effective therapeutic agent for Inflammatory Bowel Disease (IBD) for several years
AMPK↑, inhibitory effects on inflammation by regulating different mechanisms such as 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK. Increase of AMPK
MAPK↓, Mitogen-Activated Protein Kinase (MAPK), and NF-κB signaling pathways
NF-kB↓,
IL6↓, inhibiting the expression of proinflammatory genes such as IL-1, IL-6, Monocyte Chemoattractant Protein 1 (MCP1), TNF-α, Prostaglandin E2 (PGE2), and Cyclooxygenase-2 (COX-2)
MCP1↓,
PGE2↓,
COX2↓,
*ROS↓, BBR protected PC-12 cells (normal) from oxidative damage by suppressing ROS through PI3K/AKT/mTOR signaling pathways
*antiOx↑, BBR therapy improved the antioxidant function of mice intestinal tissue by enhancing the levels of glutathione peroxidase and catalase enzymes.
*GPx↑,
*Catalase↑,
AntiTum↑, Besides, BBR leaves great antitumor effects on multiple types of cancer such as breast cancer,69 bladder cancer,70 hepatocarcinoma,71 and colon cancer.72
TumCP↓, BBR exerts its antitumor activity by inhibiting proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis and metastasis
angioG↓,
Fas↑, by increasing the amounts of Fas receptor (death receptor)/FasL (Fas ligand), ROS, ATM, p53, Retinoblastoma protein (Rb), caspase-9,8,3, TNF-α, Bcl2-associated X protein (Bax), BID
FasL↑,
ROS↑,
ATM↑,
P53↑,
RB1↑,
Casp9↑,
Casp8↑,
Casp3↓,
BAX↑,
Bcl-2↓, and declining Bcl2, Bcl-X, c-IAP1 (inhibitor of apoptosis protein), X-linked inhibitor of apoptosis protein (XIAP), and Survivin levels
Bcl-xL↓,
IAP1↓,
XIAP↓,
survivin↓,
MMP2↓, Furthermore, BBR suppressed Matrix Metalloproteinase-2 (MMP-2), and MMP-9 expression.
MMP9↓,
CycB/CCNB1↓, Inhibition of cyclin B1, cdc2, cdc25c
CDC25↓,
CDC25↓,
Cyt‑c↑, BBR inhibited tumor cell proliferation and migration and induced mitochondria-mediated apoptosis pathway in Triple Negative Breast Cancer (TNBC) by: stimulating cytochrome c release from mitochondria to cytosol
MMP↓, decreased the mitochondrial membrane potential, and enabled cytochrome c release from mitochondria to cytosol
RenoP↑, BBR significantly reduced the destructive effects of cisplatin on the kidney by inhibiting autophagy, and exerted nephroprotective effects.
mTOR↓, U87 cell, Inhibition of m-TOR signaling
MDM2↓, Downregulation of MDM2
LC3II↑, Increase of LC3-II and beclin-1
ERK↓, BBR stimulated AMPK signaling, resulting in reduced extracellular signal–regulated kinase (ERK) activity and COX-2 expression in B16F-10 lung melanoma cells
COX2↓,
MMP3↓, reducing MMP-3 in SGC7901 GC and AGS cells
TGF-β↓, BBR suppressed the invasion and migration of prostate cancer PC-3 cells by inhibiting TGF-β-related signaling molecules which induced Epithelial-Mesenchymal Transition (EMT) such as Bone morphogenetic protein 7 (BMP7),
EMT↑,
ROCK1↓, inhibiting metastasis-associated proteins such as ROCK1, FAK, Ras Homolog Family Member A (RhoA), NF-κB and u-PA, leading to in vitro inhibition of MMP-1 and MMP-13.
FAK↓,
RAS↓,
Rho↓,
NF-kB↓,
uPA↓,
MMP1↓,
MMP13↓,
ChemoSen↑, recent studies have indicated that it can be used in combination with chemotherapy agents

5639- BCA,    Biochanin A Induces Apoptosis in MCF-7 Breast Cancer Cells through Mitochondrial Pathway and Pi3K/AKT Inhibition
- in-vitro, BC, NA
TumCP↓, Biochanin A inhibited cell proliferation, increased reactive oxygen species formation, and induced apoptosis.
ROS↑,
Apoptosis↑,
Bcl-2↓, Biochanin A-treated cells exhibited lower expression of the Bcl-2, p-PI3K and p-AKT and higher expression of proapoptotic genes, including Bax, Caspase-3, Caspase-9, and cytochrome c.
p‑PI3K↓,
p‑Akt↓,
BAX↑,
Casp3↑,
Casp9↑,
Cyt‑c↑,
CycD3↓, gene expression levels of cyclin D3, cyclin B1, CDK1, CDK2, and CDK4 were downregulated
CycB/CCNB1↓,
CDK1↓,
CDK2↓,
CDK4↓,
P21↑, while the expression levels of p21, p27, and p53 were significantly upregulated
p27↑,
P53↑,
tumCV↓, These results suggest that Biochanin A can suppress the viability of breast cancer cells and induce apoptosis via the mitochondrial pathway
PI3K↓, inhibition of the Pi3K/Akt signaling pathway and modulation of cell cycle markers.
Akt↓,

2718- BetA,    The anti-cancer effect of betulinic acid in u937 human leukemia cells is mediated through ROS-dependent cell cycle arrest and apoptosis
- in-vitro, AML, U937
TumCCA↑, BA exerted a significant cytotoxic effect on U937 cells through blocking cell cycle arrest at the G2/M phase and inducing apoptosis, and that the intracellular reactive oxygen species (ROS) levels increased after treatment with BA.
Apoptosis↑,
i-ROS↑,
cycA1/CCNA1↓, down-regulation of cyclin A and cyclin B1, and up-regulation of cyclin-dependent kinase inhibitor p21WAF1/CIP1 revealed the G2/M phase arrest mechanism of BA.
CycB/CCNB1↓,
P21↑,
Cyt‑c↑, BA induced the cytosolic release of cytochrome c by reducing the mitochondrial membrane potential with an increasing Bax/Bcl-2 expression ratio.
MMP↓,
Bax:Bcl2↑,
Casp9↑, BA also increased the activity of caspase-9 and -3, and subsequent degradation of the poly (ADP-ribose) polymerase.
Casp3↑,
PARP↓,
eff↓, However, quenching of ROS by N-acetyl-cysteine, an ROS scavenger, markedly abolished BA-induced G2/M arrest and apoptosis, indicating that the generation of ROS plays a key role in inhibiting the proliferation of U937 cells by BA treatment.
*antiOx↑, Accumulated evidence demonstrates that BA possesses various biological activities, including antioxidant, anti-inflammatory, hepatoprotective, and anti-tumor effects
*Inflam↓,
*hepatoP↑,
selectivity↑, BA are complex and depends on the type of cancer cells, without causing toxicity toward normal cells
NF-kB↓, Shen et al. (2019) recently reported that the suppression of the nuclear factor-kappa B pathway increased downstream oxidant effectors, thereby promoting the generation of reactive oxygen species (ROS) in BA-stimulated multiple myeloma cells.
*ROS↓, Although BA is known to have antioxidant activity that blocks the accumulation of ROS due to oxidative stress in normal cells (Cheng et al. 2019;

2719- BetA,    Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential
- in-vitro, CRC, T24/HTB-9 - in-vitro, Bladder, UMUC3 - in-vitro, Bladder, 5637
TumCD↑, BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest.
Apoptosis↑,
TumCCA↑,
CycB/CCNB1↓, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c
cycA1/CCNA1↓,
CDK2↓,
CDC25↓,
mtDam↑, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway.
BAX↑, BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9.
cl‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Snail↓, decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells.
Slug↓,
MMP9↓,
selectivity↑, Among the bladder cancer cell lines, 5637 cells were much more sensitive to BA than T24 or UMUC-3 cells under the same conditions. However, BA does not affect cell growth in normal cell lines including RAW 264.7
MMP↓, BA Induces Loss of Mitochondrial Membrane Potential (MMP, ΔΨm) in Human Bladder Cancer Cells
ROS∅, As a result, we found that BA did not affect intracellular ROS levels in all three bladder cancer cells. In addition, BA-induced cell viability inhibition was not restored by NAC pre-treatment
TumCMig↓, BA Decreases Migration and Invasion of Human Bladder Cancer Cells
TumCI↓,

5720- BF,    Acetyl-bufalin shows potent efficacy against non-small-cell lung cancer by targeting the CDK9/STAT3 signalling pathway
- in-vitro, NSCLC, NA
STAT3↓, acetyl-bufalin impaired the complex formation of CDK9 and STAT3, decreased the expressions of P-STAT3, and transcribed target genes such as cyclin B1, CDC2, MCL-1, Survivin, VEGF, BCL2
CycB/CCNB1↓,
CDC2↓,
Mcl-1↓,
survivin↓,
VEGF↓,
Bcl-2↓,
BAX↑, and it upregulated the expression levels of BAX and caspase-3 activity.
Casp3↑,

2781- CHr,  PBG,    Chrysin a promising anticancer agent: recent perspectives
- Review, Var, NA
PI3K↓, It can block Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling in different animals against various cancers
Akt↓,
mTOR↓,
MMP9↑, Chrysin strongly suppresses Matrix metalloproteinase-9 (MMP-9), Urokinase plasminogen activator (uPA) and Vascular endothelial growth factor (VEGF), i.e. factors that can cause cancer
uPA↓,
VEGF↓,
AR↓, Chrysin has the ability to suppress the androgen receptor (AR), a protein necessary for prostate cancer development and metastasis
Casp↑, starts the caspase cascade and blocks protein synthesis to kill lung cancer cells
TumMeta↓, Chrysin significantly decreased lung cancer metastasis i
TumCCA↑, Chrysin induces apoptosis and stops colon cancer cells in the G2/M cell cycle phase
angioG↓, Chrysin prevents tumor growth and cancer spread by blocking blood vessel expansion
BioAv↓, Chrysin’s solubility, accessibility and bioavailability may limit its medical use.
*hepatoP↑, As chrysin reduced oxidative stress and lipid peroxidation in rat liver cells exposed to a toxic chemical agent.
*neuroP↑, Protecting the brain against oxidative stress (GPx) may be aided by increasing levels of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx).
*SOD↑,
*GPx↑,
*ROS↓, A decrease in oxidative stress and an increase in antioxidant capacity may result from chrysin’s anti-inflammatory properties
*Inflam↓,
*Catalase↑, Supplementation with chrysin increased the activity of antioxidant enzymes like SOD and catalase and reduced the levels of oxidative stress markers like malondialdehyde (MDA) in the colon tissue of the rats.
*MDA↓, Antioxidant enzyme activity (SOD, CAT) and oxidative stress marker (MDA) levels were both enhanced by chrysin supplementation in mouse liver tissue
ROS↓, reduction of reactive oxygen species (ROS) and oxidative stress markers in the cancer cells further indicated the antioxidant activity of chrysin
BBB↑, After crossing the blood-brain barrier, it has been shown to accumulate there
Half-Life↓, The half-life of chrysin in rats is predicted to be close to 2 hours.
BioAv↑, Taking chrysin with food may increase the effectiveness of the supplement: increased by a factor of 1.8 when taken with a high-fat meal
ROS↑, In contrast to 5-FU/oxaliplatin, chrysin increases the production of reactive oxygen species (ROS), which in turn causes autophagy by stopping Akt and mTOR from doing their jobs
eff↑, mixture of chrysin and cisplatin caused the SCC-25 and CAL-27 cell lines to make more oxygen free radicals. After treatment with chrysin, cisplatin, or both, the amount of reactive oxygen species (ROS) was found to have gone up.
ROS↑, When reactive oxygen species (ROS) and calcium levels in the cytoplasm rise because of chrysin, OC cells die.
ROS↑, chrysin is the cause of death in both types of prostate cancer cells. It does this by depolarizing mitochondrial membrane potential (MMP), making reactive oxygen species (ROS), and starting lipid peroxidation.
lipid-P↑,
ER Stress↑, when chrysin is present in DU145 and PC-3 cells, the expression of a group of proteins that control ER stress goes up
NOTCH1↑, Chrysin increased the production of Notch 1 and hairy/enhancer of split 1 at the protein and mRNA levels, which stopped cells from dividing
NRF2↓, Not only did chrysin stop Nrf2 and the genes it controls from working, but it also caused MCF-7 breast cancer cells to die via apoptosis.
p‑FAK↓, After 48 hours of treatment with chrysin at amounts between 5 and 15 millimoles, p-FAK and RhoA were greatly lowered
Rho↓,
PCNA↓, Lung histology and immunoblotting studies of PCNA, COX-2, and NF-B showed that adding chrysin stopped the production of these proteins and maintained the balance of cells
COX2↓,
NF-kB↓,
PDK1↓, After the chrysin was injected, the genes PDK1, PDK3, and GLUT1 that are involved in glycolysis had less expression
PDK3↑,
GLUT1↓,
Glycolysis↓, chrysin stops glycolysis
mt-ATP↓, chrysin inhibits complex II and ATPases in the mitochondria of cancer cells
Ki-67↓, the amounts of Ki-67, which is a sign of growth, and c-Myc in the tumor tissues went down
cMyc↓,
ROCK1↓, (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) were much lower.
TOP1↓, DNA topoisomerases and histone deacetylase were inhibited, along with the synthesis of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and (IL-1 beta), while the activity of protective signaling pathways was increased
TNF-α↓,
IL1β↓,
CycB/CCNB1↓, Chrysin suppressed cyclin B1 and CDK2 production in order to stop cancerous growth.
CDK2↓,
EMT↓, chrysin treatment can also stop EMT
STAT3↓, chrysin block the STAT3 and NF-B pathways, but it also greatly reduced PD-L1 production both in vivo and in vitro.
PD-L1↓,
IL2↑, chrysin increases both the rate of T cell growth and the amount of IL-2

1145- CHr,    Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways
- in-vitro, Cerv, HeLa
tumCV↓,
BAX↑,
BID↑,
BOK↑,
APAF1↑,
TNF-α↑,
FasL↑,
Fas↑,
FADD↑,
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
Mcl-1↓,
NAIP↓,
Bcl-2↓,
CDK4↓,
CycB/CCNB1↓,
cycD1/CCND1↓,
cycE1↓,
TRAIL↑,
p‑Akt↓,
Akt↓,
mTOR↓,
PDK1↓,
BAD↓,
GSK‐3β↑,
AMPK↑, AMPKa
p27↑,
P53↑,

118- CUR,    Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145
ROS↑, WZ35 treatment for 30 min significantly induced reactive oxygen species (ROS) production in PC-3 cells.
Bcl-2↓,
PARP↑,
cDC2↓, decreased expression of CDC2, cyclinB1, and MDM2
CycB/CCNB1↓,
MDM2↓,
eff↓, Co-treatment with the ROS scavenger NAC completely abrogated the induction of WZ35 on cell apoptosis,
eIF2α↑, WZ35 treatment also induced a constant increase in the level of phosphorylated eIF2α 3 to 12 h after WZ35 treatment
ATF4↑, ATF4 expression also increased in a similar manner with p-eIF2α
CHOP↑, CHOP protein expression apparently increased 9-24 h after WZ35 treatment and peaked at 12 h
ER Stress↑, results suggest that WZ35 can induce ER stress in prostate cancer cells
TumCCA↑, WZ35 induced cell cycle arrest in G2/M phase in PC-3 cells

477- CUR,    Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells
- in-vitro, Cerv, SiHa
TumCP↓,
TumCCA↑, Inducing G2/M cell cycle arrest
Apoptosis↑,
TumAuto↑,
CycB/CCNB1↓, cyclins B1
CDC25↓,
ROS↑,
p62↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,
cl‑Casp3↑,
cl‑PARP↑,
P53↑,
P21↑,

1328- EMD,    Emodin induces apoptosis of human tongue squamous cancer SCC-4 cells through reactive oxygen species and mitochondria-dependent pathways
- in-vitro, Tong, SCC4
TumCCA↑, G2/M arrest
P21↑,
Chk2↑,
CycB/CCNB1↓,
cDC2↓,
Apoptosis↑,
Cyt‑c↑, release of cytochrome c from mitochondria
Casp9↑,
Casp3↑,
ROS↑,
MMP↓,
Bax:Bcl2↑,
ER Stress↑,

804- GAR,    Garcinol inhibits the proliferation of endometrial cancer cells by inducing cell cycle arrest
- in-vitro, EC, HEC1B - in-vitro, EC, ISH
TumCP↓,
TumCCA↑, induced ISH and HEC-1B cell cycle arrest at the G1 phase and G2/M phase, respectively
P53↑,
P21↑,
CDK2↓,
CDK4↓,
cycD1/CCND1↓,
CycB/CCNB1↓,
p‑cJun↑,

863- Lae,    Amygdalin inhibits the growth of renal cell carcinoma cells in vitro
- in-vitro, RCC, NA
TumCG↓,
TumCP↓,
TumCCA↑, cell cycle arrest in the S-phase
CDK1↓,
CycB/CCNB1↓,
E-cadherin↝,
N-cadherin↝,

2914- LT,    Therapeutic Potential of Luteolin on Cancer
- Review, Var, NA
*antiOx↑, As an antioxidant, Luteolin and its glycosides can scavenge free radicals caused by oxidative damage and chelate metal ions
*IronCh↑,
*toxicity↓, The safety profile of Luteolin has been proven by its non-toxic side effects, as the oral median lethal dose (LD50) was found to be higher than 2500 and 5000 mg/kg in mice and rats, respectively, equal to approximately 219.8−793.7 mg/kg in humans
*BioAv↓, One major problem related to the use of flavonoids for therapeutic purposes is their low bioavailability.
*BioAv↑, Resveratrol, which functions as the inhibitor of UGT1A1 and UGT1A9, significantly improved the bioavailability of Luteolin by decreasing the major glucuronidation metabolite in rats
DNAdam↑, Luteolin’s anticancer properties, which involve DNA damage, regulation of redox, and protein kinases in inhibiting cancer cell proliferation
TumCP↓,
DR5↑, Luteolin was discovered to promote apoptosis of different cancer cells by increasing Death receptors, p53, JNK, Bax, Cleaved Caspase-3/-8-/-9, and PARP expressions
P53↑,
JNK↑,
BAX↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑PARP↑,
survivin↓, downregulating proteins involved in cell cycle progression, including Survivin, Cyclin D1, Cyclin B, and CDC2, and upregulating p21
cycD1/CCND1↓,
CycB/CCNB1↓,
CDC2↓,
P21↑,
angioG↓, suppress angiogenesis in cancer cells by inhibiting the expression of some angiogenic factors, such as MMP-2, AEG-1, VEGF, and VEGFR2
MMP2↓,
AEG1↓,
VEGF↓,
VEGFR2↓,
MMP9↓, inhibit metastasis by inhibiting several proteins that function in metastasis, such as MMP-2/-9, CXCR4, PI3K/Akt, ERK1/2
CXCR4↓,
PI3K↓,
Akt↓,
ERK↓,
TumAuto↑, can promote the conversion of LC3B I to LC3B II and upregulate Beclin1 expression, thereby causing autophagy
LC3B-II↑,
EMT↓, Luteolin was identified to suppress the epithelial to mesenchymal transition by upregulating E-cadherin and downregulating N-cadherin and Wnt3 expressions.
E-cadherin↑,
N-cadherin↓,
Wnt↓,
ROS↑, DNA damage that is induced by reactive oxygen species (ROS),
NICD↓, Luteolin can block the Notch intracellular domain (NICD) that is created by the activation of the Not
p‑GSK‐3β↓, Luteolin can inhibit the phosphorylation of the GSK3β induced by Wnt, resulting in the prevention of GSK3β inhibition
iNOS↓, Luteolin in colon cancer and the complications associated with it, particularly the decreasing effect on the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)
COX2↓,
NRF2↑, Luteolin has been identified to increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a crucial transcription factor with anticarcinogenic properties related
Ca+2↑, caused loss of the mitochondrial membrane action potential, enhanced levels of mitochondrial calcium (Ca2+),
ChemoSen↑, Luteolin enhanced the effect of one of the most effective chemotherapy drugs, cisplatin, on CRC cells
ChemoSen↓, high dose of Luteolin application negatively affected the oxaliplatin-based chemotherapy in a p53-dependent manner [52]. They suggested that the flavonoids with Nrf2-activating ability might interfere with the chemotherapeutic efficacy of anticancer
IFN-γ↓, decreased the expression of interferon-gamma-(IFN-γ)
RadioS↑, suggested that Luteolin can act as a radiosensitizer, promoting apoptosis by inducing p38/ROS/caspase cascade
MDM2↓, Luteolin treatment was associated with increased p53 and p21 and decreased MDM4 expressions both in vitro and in vivo.
NOTCH1↓, Luteolin suppressed the growth of lung cancer cells, metastasis, and Notch-1 signaling pathway
AR↓, downregulating the androgen receptor (AR) expression
TIMP1↑, Luteolin inhibits the migration of U251MG and U87MG human glioblastoma cell lines by downregulating MMP-2 and MMP-9 and upregulating the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2.
TIMP2↑,
ER Stress↑, Luteolin caused oxidative stress and ER stress in the Hep3B cells,
CDK2↓, Luteolin’s ability to decrease Akt, polo-like kinase 1 (PLK1), cyclin B1, cyclin A, CDC2, cyclin-dependent kinase 2 (CDK2) and Bcl-xL
Telomerase↓, Luteolin dose-dependently inhibited the telomerase levels and caused the phosphorylation of NF-κB and the target gene of NF-κB, c-Myc to suppress the human telomerase reverse transcriptase (hTERT)
p‑NF-kB↑,
p‑cMyc↑,
hTERT/TERT↓,
RAS↓, Luteolin was found to suppress the expressions of K-Ras, H-Ras, and N-Ras, which are the activators of PI3K
YAP/TEAD↓, Luteolin caused significant inhibition of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)
TAZ↓,
NF-kB↓, Luteolin was found to have a strong inhibitory effect on the NF-κB
NRF2↓, Luteolin-loaded nanoparticles resulted in a significant reduction in the Nrf2 levels compared to Luteolin alone.
HO-1↓, The expressions of the downstream genes of Nrf2, Ho1, and MDR1 were also reduced, where inhibition of Nrf2 expression significantly increased the cell death of breast cancer cells
MDR1↓,

2916- LT,    Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies
- Review, Var, NA - Review, AD, NA - Review, Park, NA
proCasp9↓, , by inactivating proteins; such as procaspase‐9, CDC2 and cyclin B or upregulation of caspase‐9 and caspase‐3, cytochrome C, cyclin A, CDK2, and APAF‐1, in turn inducing cell cycle
CDC2↓,
CycB/CCNB1↓,
Casp9↑,
Casp3↑,
Cyt‑c↑,
cycA1/CCNA1↑,
CDK2↓, inhibit CDK2 activity
APAF1↑,
TumCCA↑,
P53↑, enhances phosphorylation of p53 and expression level of p53‐targeted downstream gene.
BAX↑, Increasing BAX protein expression; decreasing VEGF and Bcl‐2 expression it can initiate cell cycle arrest and apoptosis.
VEGF↓,
Bcl-2↓,
Apoptosis↑,
p‑Akt↓, reduce expression levels of p‐Akt, p‐EGFR, p‐Erk1/2, and p‐STAT3.
p‑EGFR↓,
p‑ERK↓,
p‑STAT3↓,
cardioP↑, Luteolin plays positive role against cardiovascular disorders by improving cardiac function
Catalase↓, It can reduce activity levels of catalase, superoxide dismutase, and GS4
SOD↓,
*BioAv↓, bioavailability of luteolin is very low. Due to the momentous first pass effect, only 4.10% was found to be available from dosage of 50 mg/kg intake of luteolin
*antiOx↑, luteolin classically exhibits antioxidant features
*ROS↓, The antioxidant potential of luteolin and its glycosides is mainly due to scavenging activity against reactive oxygen species (ROS) and nitrogen species
*NO↓,
*GSTs↑, Luteolin may also have a role in protection and enhancement of endogenous antioxidants such as glutathione‐S‐transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT)
*GSR↑,
*SOD↑,
*Catalase↑,
*lipid-P↓, Luteolin supplementation significantly suppressed the lipid peroxidation
PI3K↓, inhibits PI3K/Akt signaling pathway to induce apoptosis
Akt↓,
CDK2↓, inhibit CDK2 activity
BNIP3↑, upregulation of BNIP3 gene
hTERT/TERT↓, Suppress hTERT in MDA‐MB‐231 breast cancer cel
DR5↑, Boost DR5 expression
Beclin-1↑, Activate beclin 1
TNF-α↓, Block TNF‐α, NF‐κB, IL‐1, IL‐6,
NF-kB↓,
IL1↓,
IL6↓,
EMT↓, Suppress EMT essentially notable in cancer metastasis
FAK↓, Block EGFR‐signaling pathway and FAK activity
E-cadherin↑, increasing E‐cadherin expression by inhibiting mdm2
MDM2↓,
NOTCH↓, Inhibit NOTCH signaling
MAPK↑, Activate MAPK to inhibit tumor growt
Vim↓, downregulation of vimentin, N‐cadherin, Snail, and induction of E‐cadherin expressions
N-cadherin↓,
Snail↓,
MMP2↓, negatively regulated MMP2 and TWIST1
Twist↓,
MMP9↓, Inhibit matrix metalloproteinase‐9 expressions;
ROS↑, Induce apoptosis, reactive oxygen development, promotion of mitochondrial autophagy, loss of mitochondrial membrane potential
MMP↓,
*AChE↓, Reduce AchE activity to slow down inception of Alzheimer's disease‐like symptoms
*MMP↑, Reverse mitochondrial membrane potential dissipation
*Aβ↓, Inhibit Aβ25‐35
*neuroP↑, reduces neuronal apoptosis; inhibits Aβ generation
Trx1↑, luteolin against human bladder cancer cell line T24 was due to induction cell‐cycle arrest at G2/M, downregulation of p‐S6, suppression of cell survival, upregulation of p21 and TRX1, reduction in ROS levels.
ROS↓,
*NRF2↑, Luteolin reduced renal injury by inhibiting XO activity, modulating uric acid transporters, as well as activating Nrf2 HO‐1/NQO1 antioxidant pathways and renal SIRT1/6 cascade.
NRF2↓, Luteolin exerted anticancer effects in HT29 cells as it inhibits nuclear factor‐erythroid‐2‐related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway
*BBB↑, Luteolin can be used to treat brain cancer due to ability of this molecule to easily cross the blood–brain barrier
ChemoSen↑, In ovarian cancer cells, luteolin chemosensitizes the cells through repressing the epithelial‐mesenchymal transition markers
GutMicro↑, Luteolin was also observed to modulate gut microbiota which reduce the number of tumors in case of colorectal cancer by enhancing the number of health‐related microbiota and reduced the microbiota related to inflammation

4778- Lyco,    Lycopene exerts cytotoxic effects by mitochondrial reactive oxygen species–induced apoptosis in glioblastoma multiforme
- in-vitro, GBM, GBM8401
BBB↑, lycopene penetration across the blood-brain barrier and its induction of apoptosis, inhibiting proliferation in GBM8401 and T98G GBM cells
Apoptosis↑,
TumCP↑,
P53↑, lycopene promoted p53 upregulation and suppressed cyclins B and cyclin D, leading to cell cycle arrest through ROS-activated ERK pathways.
CycB/CCNB1↓,
cycD1/CCND1↓,
TumCCA↓,
mt-ROS↑, Lycopene induced Mito-ROS accumulation in GBM cells
TumCG↓, Lycopene inhibits the cell growth of GBM cells

4514- MAG,    Magnolol and its semi-synthetic derivatives: a comprehensive review of anti-cancer mechanisms, pharmacokinetics, and future therapeutic potential
- Review, Var, NA
AntiCan↑, garnered significant interest for its anti-cancer effects
TumCP↓, activities against cancer, affecting various aspects of cancer cell biology, such as proliferation, cell cycle, apoptosis, metastasis, angiogenesis, and signaling pathways, such as NF-κB (Nuclear factor-KappaB), MAPK (Mitogen-activated protein kinase
TumCCA↑,
TumMeta↓,
angioG↓,
NF-kB↓,
MAPK↓,
PI3K↓,
Akt↓,
mTOR↓,
BioAv↓, its low bioavailability and solubility limit its potential clinical application.
*antiOx↑, including anti-oxidant [35], anti-inflammatory, anti-bacterial [36], anti-thrombotic or anti-platelet [37], anti-stress [38], anti-anxiety, anti-Alzheimer [39], Alzheimer, anti-stroke
*Inflam↓,
*AntiAg↑,
ChemoSen↑, administration of MG enhanced the effect of cisplatin in reducing cell viability, self-renewal, and invasion activities in cancer stem cells
cycD1/CCND1↓, Downregulation of Cyclin D1/E/B1, CDK2/4
CycB/CCNB1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
p27↑, upregulation of p27
P21↑, Upregulation of p21, p53
P53↑,
PTEN↓, Inhibition of PTEN
XIAP↓, Downregulation of XIAP, c-P, and Mc1-1
Mcl-1↓,
Casp3↑, upregulation of Caspase-3/9 NF-κB activity, p-p65, p-MMP-9, and cyclin
Casp9↑,
MMP9↑, Inhibiting MMP-9 through the NF-κB pathway

4537- MAG,    Effects of magnolol on UVB-induced skin cancer development in mice and its possible mechanism of action
- in-vivo, Melanoma, NA - in-vitro, Melanoma, A431
*cl‑Casp8↑, Magnolol pretreatment increased the cleavage of caspase-8 and poly-(-ADP-ribose) polymerase (PARP), increased the expression of p21
*PARP↑,
*P21↑,
tumCV↓, Treatment of A431 cells with magnolol decreased cell viability and cell proliferation in a concentration dependent manner
TumCP↓,
TumCCA↑, Magnolol induced G2/M phase cell cycle arrest in A431 cells at 12 h
CycB/CCNB1↓, decreased expression of cell cycle proteins such as cyclin B1, cyclin A, CDK4, Cdc2
cycA1/CCNA1↓,
CDK4↓,
CDC2↓,
P21↑, simultaneous increase in the expression of Cip/p21, a cyclin-dependent kinase inhibitor.
Apoptosis↑, Magnolol induced apoptosis in vivo and in vitro with an increased cleavage of caspase-8 and PARP.

1782- MEL,    Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities
- Review, Var, NA
AntiCan↑, involvement of melatonin in different anticancer mechanisms
Apoptosis↑, apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases
TumCP↓,
TumCG↑,
TumMeta↑,
ChemoSideEff↓, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy,
radioP↑,
ChemoSen↑, augmentation of the therapeutic effects of conventional anticancer therapies
*ROS↓, directly scavenge ROS and reactive nitrogen species (RNS)
*SOD↑, melatonin can regulate the activities of several antioxidant enzymes like superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase
*GSH↑,
*GPx↑,
*Catalase↑,
Dose∅, demonstrated that 1 mM melatonin concentration is the pharmacological concentration that is able to produce anticancer effects
VEGF↓, downregulatory action on VEGF expression in human breast cancer cells
eff↑, tumor-bearing mice were treated with (10 mg/kg) of melatonin and (5 mg/kg) of cisplatin. The results have shown that melatonin was able to reduce DNA damage
Hif1a↓, MDA-MB-231-downregulation of the HIF-1α gene and protein expression coupled with the production of GLUT1, GLUT3, CA-IX, and CA-XII
GLUT1↑,
GLUT3↑,
CAIX↑,
P21↑, upregulation of p21, p27, and PTEN protein is another way of melatonin to promote cell programmed death in uterine leiomyoma
p27↑,
PTEN↑,
Warburg↓, FIGURE 3
PI3K↓, in colon cancer cells by downregulation of PI3K/AKT and NF-κB/iNOS
Akt↓,
NF-kB↓,
cycD1/CCND1↓,
CDK4↓,
CycB/CCNB1↓,
CDK4↓,
MAPK↑,
IGF-1R↓,
STAT3↓,
MMP9↓,
MMP2↓,
MMP13↓,
E-cadherin↑,
Vim↓,
RANKL↓,
JNK↑,
Bcl-2↓,
P53↑,
Casp3↑,
Casp9↑,
BAX↑,
DNArepair↑,
COX2↓,
IL6↓,
IL8↓,
NO↓,
T-Cell↑,
NK cell↑,
Treg lymp↓,
FOXP3↓,
CD4+↑,
TNF-α↑,
Th1 response↑, FIGURE 3
BioAv↝, varies 1% to 50%?
RadioS↑, melatonin’s radio-sensitizing properties
OS↑, In those individuals taking melatonin, the overall tumor regression rate and the 5-year survival were elevated

496- MF,    Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, ZR-75-1 - in-vitro, BC, T47D - in-vitro, BC, MDA-MB-231
ROS↑, LF-MFs Enhanced the ROS Levels in MCF-7 and ZR75-1 Cells
PI3K↓, and inhibited the activities of the PI3K/AKT signaling pathways in MCF-7 and ZR-75-1 cells
Akt↓,
GSK‐3β↑, LF-MF Induced MCF-7 and ZR75-1 Cells Apoptosis by Activating GSK-3β
Apoptosis↑, LF-MF Induced Breast Cancer Cell Apoptosis
cl‑PARP↑, cleaved PARP-1
cl‑Casp3↑,
BAX↑,
Bcl-2↓,
CycB/CCNB1↓, Cyclin B1
TumCCA↑, failure of the transition from the G2 phase to M phase
p‑Akt↓,
TumCP↓, LF-MF Inhibited the Proliferation of Breast Cancer Cells
selectivity↑, The viabilities of HUVECs did not markedly reduce after exposure in LF-MF at the four selected frequencies for 6, 12, 24 or 36 h
eff↓, attenuated by ROS scavenger NAC

2069- PB,    Toxic and metabolic effect of sodium butyrate on SAS tongue cancer cells: role of cell cycle deregulation and redox changes
- in-vitro, Tong, NA
TumCG↓, sodium butyrate inhibited the growth of SAS tongue cancer cells by 32% and 53% at concentrations of 1 and 2mM, respectively
ROS↑, These events were concomitant with induction of intracellular reactive oxygen species (ROS) production.
P21↑, An elevation in p21 mRNA and protein level was noted in SAS cells by sodium butyrate.
CycB/CCNB1↓, decline of cyclin Bl, cdc2 and cdc25C mRNA and protein expression in SAS cells was found after exposure to sodium butyrate
cDC2↓,
CDC25↓,
eff↓, Inclusion of N-acetyl-l-cysteine (NAC) (3mM), catalase (1000 U/ml) and dimethylthiourea (DMT, 5mM), and also SOD (500 U/ml) attenuated the sodium butyrate-induced ROS production in SAS cells.
TumCCA↑, sodium butyrate is toxic and inhibits the tongue cancer cell growth via induction of cell cycle arrest and apoptosis
Apoptosis↑,

1664- PBG,    Anticancer Activity of Propolis and Its Compounds
- Review, Var, NA
Apoptosis↑,
TumCMig↓,
TumCCA↑,
TumCP↓,
angioG↓,
P21↑, upregulating p21 and p27 expression
p27↑,
CDK1↓, thanol-extracted Cameroonian propolis increased the amount of DU145 and PC3 cells in G0/G1 phase, down-regulated cell cycle proteins (CDK1, pCDK1, and their related cyclins A and B)
p‑CDK1↓,
cycA1/CCNA1↓,
CycB/CCNB1↓,
P70S6K↓, Caffeic acid phenylethyl ester has been shown to inhibit the S6 beta-1 ribosomal protein kinase (p70S6K),
CLDN2↓, inhibition of NF-κB may be involved in the decrease of claudin-2 mRNA level
HK2↓, Chinese poplar propolis has been shown to significantly reduce the level of glycolysis at the stage of action of hexokinase 2 (HK2), phosphofructokinase (PFK), muscle isozyme pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA)
PFK↓,
PKM2↓,
LDHA↓,
TLR4↓, hinese propolis, as well as CAPE, inhibits breast cancer cell proliferation in the inflammatory microenvironment by inhibiting the Toll-like receptor 4 (TLR4) signal pathway
H3↓, Brazilian red propolis bioactive isoflavonoid, down-regulates the alpha-tubulin, tubulin in microtubules, and histone H3 genes
α-tubulin↓,
ROS↑, CAPE also affects the apoptotic intrinsic pathway by increasing ROS production
Akt↓, CAPE induces apoptosis by decreasing the levels of proteins related to carcinogenesis, including Akt, GSK3b, FOXO1, FOXO3a, NF-kB, Skp2 and cyclin D1
GSK‐3β↓,
FOXO3↓,
NF-kB↓,
cycD1/CCND1↓,
MMP↓, It was found that chrysin caused a loss of mitochondria membrane potential (MMP) while increasing the production of reactive oxygen species (ROS), cytoplasmic Ca2+ levels, and lipid peroxidation
ROS↑,
i-Ca+2↑,
lipid-P↑,
ER Stress↑, Chrysin also induced endoplasmic reticulum (ER) stress by activating unfolded protein response proteins (UPR) such as PRKR-like ER kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), and 78 kDa glucose-regulated protein (GRP78)
UPR↑,
PERK↑,
eIF2α↑,
GRP78/BiP↑,
BAX↑, CAPE activated Bax protein
PUMA↑, CAPE also significantly increased PUMA expression
ROS↑, Northeast China causes cell apoptosis in human gastric cancer cells with increased production of reactive oxygen species (ROS) and reduced mitochondrial membrane potential.
MMP↓,
Cyt‑c↑, release of cytochrome C from mitochondria to the cytoplasm is observed, as well as the activation of cleaved caspases (8, 9, and 3) and PARP
cl‑Casp8↑,
cl‑Casp8↑,
cl‑Casp3↑,
cl‑PARP↑,
eff↑, administration of Iranian propolis extract in combination with 5-fluorouracil (5-FU) significantly reduced the number of azaxymethane-induced aberrant crypt foci compared to 5-FU or propolis alone.
eff↑, Propolis may also have a positive effect on the efficacy of photodynamic therapy (PDT). enhances the intracellular accumulation of protoporphyrin IX (PpIX) in human epidermoid carcinoma cells
RadioS↑, breast cancer patients undergoing radiotherapy and supplemented with propolis had a statistically significant longer median disease-free survival time than the control group
ChemoSen↑, confirmed that propolis mouthwash is effective and safe in the treatment of chemo- or radiotherapy-induced oral mucositis in cancer patients.
eff↑, Quercetin, ferulic acid, and CAPE may also influence the MDR of cancer cells by inhibiting P-gp expression

1666- PBG,    Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer
- Review, Var, NA
ChemoSen↑, Ingredients from propolis also ”sensitize“ cancer cells to chemotherapeutic agents
TumCCA↑, cell-cycle arrest and attenuation of cancer cells proliferation
TumCP↓,
Apoptosis↑,
antiOx↓, behave as antioxidants against peroxyl and hydroxyl radicals,
ROS↑, whereas prooxidant activity is observed in the presence of Cu2+.
COX2↑, Propolis, as well as flavonoids derived from propolis, such as galangin, is a potent COX-2 inhibitor
ER(estro)↓, Some flavonoids from propolis, such as galangin, genistein, baicalein, hesperetin, naringenin, and quercetin, suppressed the proliferation of an estrogen receptor (ER)
cycA1/CCNA1↓, by suppressing expressions of cyclin A, cyclin B, and Cdk2 and by stopping proliferation at the G2 phase, by increasing levels of p21 and p27 proteins, and through the inhibition of telomerase reverse transcriptase (hTERT),
CycB/CCNB1↓,
CDK2↓,
P21↑,
p27↑,
hTERT/TERT↓, leukemia cells, propolis successfully reduced hTERT mRNA expression
HDAC↓, by suppressing expressions of cyclin A, cyclin B, and Cdk2 and by stopping proliferation at the G2 phase, by increasing levels of p21 and p27 proteins, and through the inhibition of telomerase reverse transcriptase (hTERT),
ROS⇅, Mexican propolis, demonstrated both pro- and anti-inflammatory effects, depending on the dose applied
Dose?, Mexican propolis, demonstrated both pro- and anti-inflammatory effects, depending on the dose applied
ROS↓, By scavenging free radicals, chelating metal ions (mainly iron and copper), and stimulating endogenous antioxidant defenses, propolis and its flavonoids directly attenuate the generation of ROS
ROS↑, Romanian propolis [99], exhibits prooxidant properties at high concentrations, by mobilizing endogenous copper ions and DNA-associated copper in cells.
DNAdam↑, propolis, i.e., its polyphenolic components, may induce DNA damage in the presence of transition metal ions.
ChemoSen↑, Algerian propolis + doxorubicin decreased cell viability, prevented cell proliferation and cell cycle progression, induced apoptosis by activating caspase-3 and -9 activities, and increased the accumulation of chemotherapeutic drugs in MDA-MB-231 cel
LOX1↓, propolis components inhibited the LOX pathway
lipid-P↓, Croatian propolis improved psoriatic-like skin lesions induced by irritant agents n-hexyl salicylate or di-n-propyl disulfide by decreasing the extent of lipid peroxidation
NO↑, Taken together, propolis may increase the phagocytic index, NO production, and production of IgG antibodies
Igs↑,
NK cell↑, propolis treatment for 3 days increases the cytotoxic activity of NK cells against murine lymphoma.
MMPs↓, extracts of propolis containing artepillin C and CAPE decreased the formation of new vessels and expression of MMPs and VEGF in various cancer cells
VEGF↓,
Hif1a↓, Brazilian green propolis inhibit the expression of the hypoxia-inducible factor-1 (HIF-1) protein and HIF-1 downstream targets such as glucose transporter 1, hexokinase 2, and VEGF-A
GLUT1↓,
HK2↓,
selectivity↑, Portuguese propolis was selectively toxic against malignant cells.
RadioS↑, propolis increased the lifespan of mice that received the radiotherapy with gamma rays
GlucoseCon↓, Portuguese propolis disturbed the glycolytic metabolism of human colorectal cancer cells, as evidenced by a decrease in glucose consumption and lactate production
lactateProd↓,
eff↓, Furthermore, different pesticides or heavy metals can be found in propolis, which can cause unwanted side effects.
*BioAv↓, Due to the low bioavailability and clinical efficacy of propolis and its flavonoids, their biomedical applications remain limited.

3256- PBG,    Mechanisms of Apoptosis and Cell Cycle Arrest Induced by Propolis in Cancer Therapy
- Review, Var, NA
TumCCA↑, The flavonoids and phenolic acids in propolis also play critical roles in halting cell proliferation by arresting the cell cycle at G0/G1 or G2/M phases, often through the downregulation of cyclins and cyclin-dependent kinases (CDKs).
CDK2↓, CAPE attenuates CDK2/4 activity through Akt–Skp2 signalling in CRPC cells
CDK4↓,
cycA1/CCNA1↓, Whole-extract propolis lowered cyclin A and B1 in U-937 leukaemia cells
CycB/CCNB1↓,

2948- PL,    The promising potential of piperlongumine as an emerging therapeutics for cancer
- Review, Var, NA
tumCV↓, inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases,
TumCP↓,
TumCI↓,
angioG↓,
EMT↓,
TumMeta↓,
*hepatoP↑, A study demonstrated the hepatoprotective effects of P. longum via decreasing the rate of lipid peroxidation and increasing glutathione (GSH) levels
*lipid-P↓,
*GSH↑,
cardioP↑, cardioprotective effect
CycB/CCNB1↓, downregulated the mRNA expression of the cell cycle regulatory genes such as cyclin B1, cyclin D1, cyclin-dependent kinases (CDK)-1, CDK4, CDK6, and proliferating cell nuclear antigen (PCNA)
cycD1/CCND1↓,
CDK2↓,
CDK1↓,
CDK4↓,
CDK6↓,
PCNA↓,
Akt↓, suppression of the Akt/mTOR pathway by PL was also associated with the partial inhibition of glycolysis
mTOR↓,
Glycolysis↓,
NF-kB↓, Suppression of the NF-κB signaling pathway and its related genes by PL was reported in different cancers
IKKα↓, inactivation of the inhibitor of NF-κB kinase subunit beta (IKKβ)
JAK1↓, PL efficiently inhibited cell proliferation, invasion, and migration by blocking the JAK1,2/STAT3 signaling pathway
JAK2↓,
STAT3↓,
ERK↓, PL also negatively regulates ERK1/2 signaling pathways, thereby suppressing the level of c-Fos in CRC cells
cFos↓,
Slug↓, PL was found to downregulate slug and upregulate E-cadherin and inhibited epithelial-mesenchymal transition (EMT) in breast cancer cells
E-cadherin↑,
TOP2↓, ↓topoisomerase II, ↑p53, ↑p21, ↓Bcl-2, ↑Bax, ↑Cyt C, ↑caspase-3, ↑caspase-7, ↑caspase-8
P53↑,
P21↑,
Bcl-2↓,
BAX↑,
Casp3↑,
Casp7↑,
Casp8↑,
p‑HER2/EBBR2↓, ↓p-HER1, ↓p-HER2, ↓p-HER3
HO-1↑, ↑Apoptosis, ↑HO-1, ↑Nrf2
NRF2↑,
BIM↑, ↑BIM, ↑cleaved caspase-9 and caspase-3, ↓p-FOXO3A, ↓p-Akt
p‑FOXO3↓,
Sp1/3/4↓, ↑apoptosis, ↑ROS, ↓Sp1, ↓Sp3, ↓Sp4, ↓cMyc, ↓EGFR, ↓survivin, ↓cMET
cMyc↓,
EGFR↓,
survivin↓,
cMET↓,
NQO1↑, G2/M phase arrest, ↑apoptosis, ↑ROS, ↓p-Akt, ↑Bad, ↓Bcl-2, ↑NQO1, ↑HO-1, ↑SOD2, ↑p21, ↑p-ERK, ↑p-JNK,
SOD2↑,
TrxR↓, G2/M cell cycle arrest, ↑apoptosis, ↑ROS, ↓GSH, ↓TrxR
MDM2↓, ↑ROS, ↓MDM-2, ↓cyclin B1, ↓Cdc2, G2/M phase arrest, ↑p-eIF2α, ↑ATF4, KATO III ↑CHOP, ↑apoptosis
p‑eIF2α↑,
ATF4↑,
CHOP↑,
MDA↑, ↑ROS, ↓TrxR1, ↑cleaved caspase-3, ↑CHOP, ↑MDA
Ki-67↓, ↓Ki-67, ↓MMP-9, ↓Twist,
MMP9↓,
Twist↓,
SOX2↓, ↓SOX2, ↓NANOG, ↓Oct-4, ↑E-cadherin, ↑CK18, ↓N-cadherin, ↓vimentin, ↓snail, ↓slug
Nanog↓,
OCT4↓,
N-cadherin↓,
Vim↓,
Snail↓,
TumW↓, ↓Tumor weight, ↓tumor growth
TumCG↓,
HK2↓, ↓HK2
RB1↓, ↓Rb
IL6↓, ↓IL-6, ↓IL-8,
IL8↓,
SOD1↑, ↑SOD1
RadioS↑, ombination with PL, very low intensity of radiation is found to be effective in cancer cells
ChemoSen↑, PL as a chemosensitizer which sensitized the cancer cells towards the commercially available chemotherapeutics
toxicity↓, PL does not have any adverse effect on the normal functioning of the liver and kidney.
Sp1/3/4↓, In vitro SKBR3 ↓Sp1, ↓Sp3, ↓Sp4
GSH↓, In vitro MCF-7 ↓CDK1, G2/M phase arrest ↓CDK4, ↓CDK6, ↓PCNA, ↓p-CDK1, ↑cyclin B1, ↑ROS, ↓GSH, ↓p-IκBα,
SOD↑, In vitro PANC-1, MIA PaCa-2 ↑ROS, ↑SOD1, ↑GSTP1, ↑HO-1

5163- PLB,    Plumbagin suppresses epithelial to mesenchymal transition and stemness via inhibiting Nrf2-mediated signaling pathway in human tongue squamous cell carcinoma cells
- in-vitro, SCC, SCC25
TumCP↓, PLB inhibited cell proliferation, activated death receptor-mediated apoptotic pathway,
NRF2↓, PLB induces intracellular ROS generation and regulates redox homeostasis via suppressing Nrf2-mediated oxidative signaling pathway in SCC25 cells
TumCCA↑, PLB markedly induced cell cycle arrest at G2/M phase and extrinsic apoptosis
EMT↓, and inhibited epithelial to mesenchymal transition (EMT) and stemness in SCC25 cells.
CSCs↓,
eff↓, Of note, N-acetyl-l-cysteine (NAC) and l-glutathione (GSH) abolished the effects of PLB on cell cycle arrest, apoptosis induction, EMT inhibition, and stemness a
ROS↑, PLB on ROS generation-related molecules
CycB/CCNB1↓, PLB induces G2/M arrest in SCC25 cells via downregulation of cyclin B1, CDK1/cdc2, and cdc25
CDK1↓,
CDK2↓,
CDC25↓,
Vim↓, PLB inhibited the expression of vimentin in a concentration- and time-dependent manner
OCT4↓, PLB significantly decreased the expression level of Oct-4, Sox-2, Nanog, and Bmi-1.
SOX2↓,
Nanog↓,
BMI1↓,
NQO1↓, The expression levels of NQO1, GST, and HSP90 were all markedly decreased
GSTA1↓,
HSP90↓,
toxicity↓, PLB exhibits anticancer activities with minimal side effect in vitro and in vivo,

5162- PLB,    Plumbagin induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human melanoma A375.S2 cells
- vitro+vivo, Melanoma, A172
TumCG↓, Plumbagin exhibited effective cell growth inhibition by inducing cancer cells to undergo S-G2/M phase arrest and apoptosis.
TumCCA↑,
Apoptosis↑,
P21↑, Blockade of cell cycle was associated with increased levels of p21, and reduced amounts of cyclin B1, cyclin A, Cdc2, and Cdc25C.
CycB/CCNB1↓,
cycA1/CCNA1↓,
CDC2↓,
CDC25↑,
Bax:Bcl2↑, Plumbagin triggered the mitochondrial apoptotic pathway indicated by a change in Bax/Bcl-2 ratios, resulting in caspase-9 activation
Casp9↑,
ROS↑, generation of ROS is a critical mediator in plumbagin-induced cell growth inhibition.
JNK↑, Plumbagin increased the activation of apoptosis signal-regulating kinase 1, JNK and extracellular signal-regulated kinase 1/2 (ERK1/2), but not p38
ERK↑,
eff↓, antioxidants vitamin C and catalase significantly decreased plumbagin-mediated c-Jun N-terminal kinase (JNK) activation and apoptosis.

5161- PLB,    Plumbagin induces G2/M arrest, apoptosis, and autophagy via p38 MAPK- and PI3K/Akt/mTOR-mediated pathways in human tongue squamous cell carcinoma cells
- in-vitro, SCC, SCC25
TumCCA↑, PLB exerted potent inducing effects on cell cycle arrest, apoptosis, and autophagy in SCC25 cells
Apoptosis↑,
TumAuto↑,
Bcl-2↓, PLB decreased the expression of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl)
Bcl-xL↓,
BAX↑, while increasing the expression level of the pro-apoptotic protein Bcl-2-associated X protein (Bax) in SCC25 cells
PI3K↓, PLB inhibited phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β), and p38 mitogen-activated protein kinase (p38 MAPK)
Akt↓,
mTOR↓,
GSK‐3β↓,
MAPK↓,
ROS↑, PLB induced intracellular reactive oxygen species (ROS) generation
eff↓, and this effect was attenuated by l-glutathione (GSH) and n-acetyl-l-cysteine (NAC).
CDC2↓, PLB downregulates the expression of Cdc2 and cyclin B1 while upregulating the expression of p21 Waf1/Cip1, p27 Kip1, and p53 in SCC25 cells
CycB/CCNB1↓,
P21↑,
p27↑,
P53↑,
Casp9↑, this activates caspase 9 and caspase 3 in a positive feedback manner.
Casp3↑,

66- QC,    Emerging impact of quercetin in the treatment of prostate cancer
- Review, Pca, NA
CycB/CCNB1↓, quercetin has a role in the reduction of cyclin B1 and CDK1 levels,
CDK1↓,
EMT↓, quercetin suppresses epithelial to mesenchymal transition (EMT) and cell proliferation through modulation of Sonic Hedgehog signaling pathway
PI3K↓, Inhibitory effects of quercetin on other pathways such as PI3K, MAPK and WNT pathways have also been validated in cervical cancer
MAPK↓,
Wnt/(β-catenin)↓, wnt
PSA↓,
VEGF↓,
PARP↑,
Casp3↑,
Casp9↑,
DR5↑,
ROS⇅,
Shh↓,
P53↑, figure 1
P21↑, quercetin regulates p21 expression
EGFR↓,
TumCCA↑, quercetin has cell-specific anti-proliferative impacts via stimulation of cell cycle arrest at the G1 stage.
ROS↑, quercetin has been shown to suppress carcinogenesis through various mechanisms including affecting cell proliferation, production of reactive oxygen species and expression of miR-21
miR-21↓,
TumCP↓,
selectivity↑, In breast cancer cells, quercetin inhibits cell proliferation without exerting any cytotoxic impact on normal breast epithelium
PDGF↓, figure 1
EGF↓,
TNF-α↓,
VEGFR2↓,
mTOR↓,
cMyc↓,
MMPs↓,
GRP78/BiP↑,
CHOP↑,

54- QC,    Quercetin‑3‑methyl ether suppresses human breast cancer stem cell formation by inhibiting the Notch1 and PI3K/Akt signaling pathways
- in-vitro, BC, MCF-7
EMT↓, led to the repression of EMT promotion
E-cadherin↑,
Vim↓,
MMP2↓,
NOTCH1↓, This agent also inhibited Notch1 and PI3K/Akt signalin
PI3K/Akt↓,
PI3k/Akt/mTOR↓,
p‑Akt↓,
EZH2↓, Querectin-3-methyl ether downregulates Notch1, PI3K-AKT and EZH2 signals in breast cancer cells
H3K27ac↓, quercetin-3-methyl ether considerably decreased H3K27 methylation
TumCCA↑, cell cycle dysregulation
CSCs↓, which resulted in the downregulation of protein markers associated with cell cycle, apoptosis, stem cell pluripotency, and self-renewal, including CDK1, Cyclin B1, Bcl-xl, Bcl-2, Sox2 and Nanog
CDK1↓,
CycB/CCNB1↓,
Bcl-xL↓,
Bcl-2↓,
Nanog↓,
H3↓, Treatment with quercetin‑3‑methyl ether alone markedly suppressed the levels of tri‑methyl histone H3 (Lys27)

49- QC,    Plasma rich in quercetin metabolites induces G2/M arrest by upregulating PPAR-γ expression in human A549 lung cancer cells
- in-vitro, Lung, A549
CDK1↓, significantly suppressed the effects of 10 % QMP on cell proliferation and on the expression of cyclin B and cdk1. T
CycB/CCNB1↓,
PPARγ↑, activation of PPAR- γ plays an important role, at least in part, in the antiproliferative effects of quercetin metabolites.

84- QC,    Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression
- in-vitro, Pca, PC3
P21↑, Addition of quercetin led to substantial decrease in the expression of Cdc2/Cdk-1, cyclin B1 and phosphorylated pRb and increase in p21.
cDC2↓, Cdc2/Cdk-1
CDK1↓, Cdc2/Cdk-1
CycB/CCNB1↓,
Casp3↑,
Bcl-2↓,
Bcl-xL↓, Apoptosis markers like Bcl-2 and Bcl-X(L) were significantly decreased and Bax and caspase-3 were increased.
BAX↑,
pRB↓,
TumCCA↑, Flowcytometric analysis showed that quercetin blocks G2-M transition, with significant induction of apoptosis.
Apoptosis↑,

913- QC,    Effects of low dose quercetin: Cancer cell-specific inhibition of cell cycle progression
- in-vitro, BC, SkBr3 - in-vitro, BC, MDA-MB-435
TumCP↓,
TumCCA↑, arrest at the G1 phase
DNAdam↑, mild DNA damage
Chk2↑,
CycB/CCNB1↓, cyclin B1
CDK1↓,
tumCV↓, 94% viability with 10uM
p‑RB1↓, Rb
P21↑,

3354- QC,    Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine
- Review, Var, NA
*ROS↓, quercetin is the most effective free radical scavenger in the flavonoid family
*IronCh↓, Chelating metal ions: related studies have confirmed that quercetin can induce Cu2+ and Fe2+ to play an antioxidant role through catechol in its structure.
*lipid-P↓, quercetin could inhibit Fe2+-induced lipid peroxidation by binding Fe2+ a
*GSH↑, regulation of glutathione levels to enhance antioxidant capacity.
*NRF2↑, quercetin upregulates the expression of Nrf2 and nuclear transfer by activating the intracellular p38 MAPK pathway, increasing the level of intracellular GSH
TumCCA↑, human leukaemia U937 cells, quercetin induces cell cycle arrest at G2 (late DNA synthesis phase)
ER Stress↑, quercetin can induce ER stress and promote the release of p53, thereby inhibiting the activities of CDK2, cyclin A, and cyclin B, thereby causing MCF-7 breast cancer cells to stagnate in the S phase.
P53↑,
CDK2↓,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓, downregulation of cyclins E and D, PNCA, and Cdk-2 protein expression and increased expressions of p21 and p27
cycD1/CCND1↓,
PCNA↓,
P21↑,
p27↑,
PI3K↓, quercetin inhibited the PI3K/AKT/mTOR and STAT3 pathways in PEL, which downregulated the expression of survival cell proteins such as c-FLIP, cyclin D1, and cMyc.
Akt↓,
mTOR↓,
STAT3↓, in excess of 20 μM by inhibiting STAT3 signalling
cFLIP↓,
cMyc↓,
survivin↓, Lung cancer [27] ↓ Survivin ↑DR5
DR5↓,
*Inflam↓, Quercetin has been confirmed to be a long-acting anti-inflammatory substance in flavonoids
*IL6↓, inhibit IL-8 is stronger and can inhibit IL-6 and increase cytosolic calcium levels
*IL8↓,
COX2↓, inhibit the enzymes that produce inflammation (cyclooxygenase (COX) and lipoxygenase (LOX))
5LO↓,
*cardioP↑, The protective mechanism of quercetin on the cardiovascular system
*FASN↓, 25 μM, within 30 minutes could inhibit the synthesis of fatty acids.
*AntiAg↑, quercetin helps reduce lipid peroxidation, platelet aggregation, and capillary permeability
*MDA↓, quercetin can decrease the levels of malondialdehyde (MDA)

3343- QC,    Quercetin, a Flavonoid with Great Pharmacological Capacity
- Review, Var, NA - Review, AD, NA - Review, Arthritis, NA
*antiOx↑, Quercetin has a potent antioxidant capacity, being able to capture reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive chlorine species (ROC),which act as reducing agents by chelating transition-metal ions.
*ROS↓, Quercetin is a potent scavenger of reactive oxygen species (ROS), protecting the organism against oxidative stress
*angioG↓,
*Inflam↓, anti-inflammatory properties; the ability to protect low-density lipoprotein (LDL) oxidation, and the ability to inhibit angiogenesis;
*BioAv↓, It is known that the bioavailability of quercetin is usually relatively low (0.17–7 μg/mL), less than 10% of what is consumed, due to its poor water solubility (hydrophobicity), chemical stability, and absorption profile.
*Half-Life↑, their slow elimination since their half-life ranges from 11 to 48 h, which could favor their accumulation in plasma after repeated intakes
*GSH↑, Animal and cell studies have demonstrated that quercetin induces the synthesis of GSH
*SOD↑, increase in the expression of superoxide dismutase (SOD), catalase (CAT), and GSH with quercetin pretreatment
*Catalase↑,
*Nrf1↑, quercetin accomplishes this process involves increasing the activity of the nuclear factor erythroid 2-related factor 2 (NRF2), enhancing its binding to the ARE, reducing its degradation
*BP↓, quercetin has been shown to inhibit ACE activity, reducing blood pressure
*cardioP↑, quercetin has positive effects on cardiovascular diseases
*IL10↓, Under the influence of quercetin, the levels of interleukin 10 (IL-10), IL-1β, and TNF-α were reduced.
*TNF-α↓,
*Aβ↓, quercetin’s ability to modulate the enzyme activity in clearing amyloid-beta (Aβ) plaques, a hallmark of AD pathology.
*GSK‐3β↓, quercetin can inhibit the activity of glycogen synthase kinase 3β,
*tau↓, thus reducing tau aggregation and neurofibrillary tangles in the brain
*neuroP↑,
*Pain↓, quercetin reduces pain and inflammation associated with arthritis
*COX2↓, quercetin included the inhibition of oxidative stress, production of cytokines such as cyclooxygenase-2 (COX-2) and proteoglycan degradation, and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) (Nrf2/HO-1)
*NRF2↑,
*HO-1↑,
*IL1β↓, Mechanisms included decreased levels of TNF-α, IL-1β, IL-17, and monocyte chemoattractant protein-1 (MCP-1)
*IL17↓,
*MCP1↓,
PKCδ↓, studies with human leukemia 60 (HL-60) cells report that concentrations between 20 and 30 µM are sufficient to exert an inhibitory effect on cytosolic PKC activity and membrane tyrosine protein kinase (TPK) activity.
ERK↓, 50 µM resulted in the blockade of the extracellular signal-regulated kinases (ERK1/2) pathway
BAX↓, higher doses (75–100 µM) were used, as these doses reduced the expression of proapoptotic factors such as Bcl-2-associated X protein (Bax) and caspases 3 and 9
cMyc↓, induce apoptosis at concentrations of 80 µM and also causes a downregulation of cellular myelocytomatosis (c-myc) and Kirsten RAt sarcoma (K-ras) oncogenes
KRAS↓,
ROS↓, compound’s antioxidative effect changes entirely to a prooxidant effect at high concentrations, which induces selective cytotoxicity
selectivity↑, On the other hand, when noncancerous cells are exposed to quercetin, it exerts cytoprotective effects;
tumCV↓, decrease cell viability in human glioma cultures of the U-118 MG cell line as well as an increase in death by apoptosis and cell arrest at the G2 checkpoint of the cell cycle.
Apoptosis↑,
TumCCA↑,
eff↑, quercetin combined with doxorubicin can induce multinucleation of invasive tumor cells, downregulate P-glycoprotein (P-gp) expression, increase cell sensitivity to doxorubicin,
P-gp↓,
eff↑, resveratrol, quercetin, and catechin can effectively block the cell cycle and reduce cell proliferation in vivo
eff↑, cotreatment with epigallocatechin gallate (EGCG) inhibited catechol-O-methyltransferase (COMT) activity, decreasing COMT protein content and thereby arresting the cell cycle of PC-3 human prostate cancer cells
eff↑, synergistic treatment of tamoxifen and quercetin was also able to inhibit prostate tumor formation by regulating angiogenesis
eff↑, coadministration of 2.5 μM of EGCG, genistein, and quercetin suppressed the cell proliferation of a prostate cancer cell line (CWR22Rv1) by controlling androgen receptor and NAD (P)H: quinone oxidoreductase 1 (NQO1) expression
CycB/CCNB1↓, It can also downregulate cyclin B1 and cyclin-dependent kinase-1 (CDK-1),
CDK1↓,
CDK4↓, quercetin causes a decrease in cyclins D1/Cdk4 and E/Cdk2 and an increase in p21 in vascular smooth muscle cells
CDK2↓,
TOP2↓, quercetin is known to be a potent inhibitor of topoisomerase II (TopoII), a cell cycle-associated enzyme necessary for DNA replication
Cyt‑c↑, quercetin can induce apoptosis (cell death) through caspase-3 and caspase-9 activation, cytochrome c release, and poly ADP ribose polymerase (PARP) cleavage
cl‑PARP↑,
MMP↓, quercetin induces the loss of mitochondrial membrane potential, leading to the activation of the caspase cascade and cleavage of PARP.
HSP70/HSPA5↓, apoptotic effects of quercetin may result from the inhibition of HSP kinases, followed by the downregulation of HSP-70 and HSP-90 protein expression
HSP90↓,
MDM2↓, (MDM2), an onco-protein that promotes p53 destruction, can be inhibited by quercetin
RAS↓, quercetin can prevent Ras proteins from being expressed. In one study, quercetin was found to inhibit the expression of Harvey rat sarcoma (H-Ras), K-Ras, and neuroblastoma rat sarcoma (N-Ras) in human breast cancer cells,
eff↑, there was a substantial difference in EMT markers such as vimentin, N-cadherin, Snail, Slug, Twist, and E-cadherin protein expression in response to AuNPs-Qu-5, inhibiting the migration and invasion of MCF-7 and MDA-MB cells

3369- QC,    Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects
- Review, Pca, NA
FAK↓, Quercetin can inhibit HGF-induced melanoma cell migration by inhibiting the activation of c-Met and its downstream Gabl, FAK and PAK [84]
TumCCA↑, stimulation of cell cycle arrest at the G1 stage
p‑pRB↓, mediated through regulation of p21 CDK inhibitor and suppression of pRb phosphorylation resulting in E2F1 sequestering.
CDK2↑, low dose of quercetin has brought minor DNA injury and Chk2 induction
CycB/CCNB1↓, quercetin has a role in the reduction of cyclin B1 and CDK1 levels,
CDK1↓,
EMT↓, quercetin suppresses epithelial to mesenchymal transition (EMT) and cell proliferation through modulation of Sonic Hedgehog signaling pathway
PI3K↓, quercetin on other pathways such as PI3K, MAPK and WNT pathways have also been validated in cervical cancer
MAPK↓,
Wnt↓,
ROS↑, colorectal cancer, quercetin has been shown to suppress carcinogenesis through various mechanisms including affecting cell proliferation, production of reactive oxygen species and expression of miR-21
miR-21↑,
Akt↓, Figure 1 anti-cancer mechanisms
NF-kB↓,
FasL↑,
Bak↑,
BAX↑,
Bcl-2↓,
Casp3↓,
Casp9↑,
P53↑,
p38↑,
MAPK↑,
Cyt‑c↑,
PARP↓,
CHOP↑,
ROS↓,
LDH↑,
GRP78/BiP↑,
ERK↑,
MDA↓,
SOD↑,
GSH↑,
NRF2↑,
VEGF↓,
PDGF↓,
EGF↓,
FGF↓,
TNF-α↓,
TGF-β↓,
VEGFR2↓,
EGFR↓,
FGFR1↓,
mTOR↓,
cMyc↓,
MMPs↓,
LC3B-II↑,
Beclin-1↑,
IL1β↓,
CRP↓,
IL10↓,
COX2↓,
IL6↓,
TLR4↓,
Shh↓,
HER2/EBBR2↓,
NOTCH↓,
DR5↑, quercetin has enhanced DR5 expression in prostate cancer cells
HSP70/HSPA5↓, Quercetin has also suppressed the upsurge of hsp70 expression in prostate cancer cells following heat treatment and enhanced the quantity of subG1 cells
CSCs↓, Quercetin could also suppress cancer stem cell attributes and metastatic aptitude of isolated prostate cancer cells through modulating JNK signaling pathway
angioG↓, Quercetin inhibits angiogenesis-mediated of human prostate cancer cells through negatively modulating angiogenic factors (TGF-β, VEGF, PDGF, EGF, bFGF, Ang-1, Ang-2, MMP-2, and MMP-9)
MMP2↓,
MMP9↓,
IGFBP3↑, Quercetin via increasing the level of IGFBP-3 could induce apoptosis in PC-3 cells
uPA↓, Quercetin through decreasing uPA and uPAR expression and suppressing cell survival protein and Ras/Raf signaling molecules could decrease prostate cancer progression
uPAR↓,
RAS↓,
Raf↓,
TSP-1↑, Quercetin through TSP-1 enhancement could effectively inhibit angiogenesis

3054- RES,    Resveratrol induced reactive oxygen species and endoplasmic reticulum stress-mediated apoptosis, and cell cycle arrest in the A375SM malignant melanoma cell line
- in-vitro, Melanoma, A375
TumCG↓, Treating A375SM cells with resveratrol resulted in a decrease in cell growth.
P21↑, resveratrol was observed to increase the gene expression levels of p21 and p27, as well as decrease the gene expression of cyclin B.
p27↑,
CycB/CCNB1↓,
ROS↑, generation of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress were confirmed at the cellular and protein levels
ER Stress↑,
p‑p38↑, Resveratrol induced the ROS-p38-p53 pathway by increasing the gene expression of phosphorylated p38 mitogen-activated protein kinase
P53↑, while it induced the p53 and ER stress pathway by increasing the gene expression levels of phosphorylated eukaryotic initiation factor 2α and C/EBP homologous protein.
p‑eIF2α↑,
EP4↑,
CHOP↑,
Bcl-2↓, downregulating B-cell lymphoma-2 (Bcl-2) expression and upregulating Bcl-2-associated X protein expression
BAX↓,
TumCCA↑, Resveratrol induced cell cycle arrest of melanoma cell line
NRF2↓, the decrease in Nrf2 expression caused by resveratrol may prevent the development of such resistance and thereby increase the sensitivity of melanoma cells to chemotherapy.
ChemoSen↑,
GSH↓, (GSH/GSSG) ratio was not measured, it can easily be assumed that the increased ROS generation by resveratrol reduced the GSH/GSSG ratio compared with the control

1726- SFN,    Sulforaphane: A Broccoli Bioactive Phytocompound with Cancer Preventive Potential
- Review, Var, NA
Dose↝, Most clinical trials utilize doses of GFN ranging from 25 to 800 μmol , translating to about 65–2105 g raw broccoli or 3/4 to 23 cups of raw broccoli.
eff↝, SFN-rich powders have been made by drying out broccoli sprout
IL1β↓,
IL6↓,
IL12↓,
TNF-α↓,
COX2↓,
CXCR4↓,
MPO↓,
HSP70/HSPA5↓,
HSP90↓,
VCAM-1↓,
IKKα↓,
NF-kB↓,
HO-1↑,
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
cl‑PARP↑,
Cyt‑c↑,
Diablo↑,
CHOP↑,
survivin↓,
XIAP↓,
p38↑,
Fas↑,
PUMA↑,
VEGF↓,
Hif1a↓,
Twist↓,
Zeb1↓,
Vim↓,
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Snail↓,
CD44↓,
cycD1/CCND1↓,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDK4↓,
CDK6↓,
p50↓,
P53↑,
P21↑,
GSH↑,
SOD↑,
GSTs↑,
mTOR↓,
Akt↓,
PI3K↓,
β-catenin/ZEB1↓,
IGF-1↓,
cMyc↓,
CSCs↓, Inhibited TS-induced, CSC-like properties

3301- SIL,    Critical review of therapeutic potential of silymarin in cancer: A bioactive polyphenolic flavonoid
- Review, Var, NA
Inflam↓, graphical abstract
TumCCA↑,
Apoptosis↓,
TumMeta↓,
TumCG↓,
angioG↓,
chemoP↑, The chemo-protective effects of silymarin and silibinin propose that they could be applied to decrease the side effects and increase the anti-tumor effects of chemotherapy and radiotherapy in different types of cancers.
radioP↑,
p‑ERK↓, fig 2
p‑p38↓,
p‑JNK↓,
P53↑,
Bcl-2↓,
Bcl-xL↓,
TGF-β↓,
MMP2↓,
MMP9↓,
E-cadherin↑,
Wnt↓,
Vim↓,
VEGF↓,
IL6↓,
STAT3↓,
*ROS↓,
IL1β↓,
PGE2↓,
CDK1↓, Causes cell cycle arrest by down-regulating CDK1, cyclinB1, survivin, Bcl-xl, Mcl-1 and activating caspase 3 and caspase 9,
CycB/CCNB1↓,
survivin↓,
Mcl-1↓,
Casp3↑,
Casp9↑,
cMyc↓, Silibinin treatment diminishes c-MYC
COX2↓, Silibinin considerably down-regulated the expression of COX-2, HIF-1α, VEGF, Ang-2, Ang-4, MMP-2, MMP-9, CCR-2 and CXCR-4
Hif1a↓,
CXCR4↓,
CSCs↓, HCT-116 cells, Induction of apoptosis, suppression of migration, elimination of CSCs. Attenuation of EMT via decreased expression of N- cadherin and vimentin and increased expression of (E-cadherin).
EMT↓,
N-cadherin↓,
PCNA↓, Decrease in PCNA and cyclin D1 level.
cycD1/CCND1↓,
ROS↑, Hepatocellular carcinoma: Silymarin nanoemulsion reduced the cell viability and increased ROS intensity and chromatin condensation.
eff↑, Silymarin + Curcumin
eff↑, Silibinin + Metformin
eff↑, Silibinin + 1, 25-vitamin D3
HER2/EBBR2↓, Significant down regulation of HER2 by 150 and 250 µM of silybin after 24, 48 and 72 h.


Showing Research Papers: 1 to 50 of 51
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 51

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   ATF3↑, 1,   Catalase↓, 1,   GSH↓, 4,   GSH↑, 2,   GSR↑, 1,   GSTA1↓, 1,   GSTs↑, 1,   HO-1↓, 1,   HO-1↑, 3,   lipid-P↓, 1,   lipid-P↑, 3,   MDA↓, 1,   MDA↑, 1,   MPO↓, 1,   NQO1↓, 1,   NQO1↑, 2,   NRF2↓, 5,   NRF2↑, 4,   ROS↓, 5,   ROS↑, 28,   ROS⇅, 2,   ROS∅, 1,   i-ROS↑, 1,   mt-ROS↑, 1,   SIRT3↑, 1,   SOD↓, 1,   SOD↑, 3,   SOD1↑, 1,   SOD2↑, 1,   Trx1↑, 1,   TrxR↓, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↑, 1,   ATP↓, 1,   mt-ATP↓, 1,   BOK↑, 1,   CDC2↓, 8,   CDC25↓, 8,   CDC25↑, 1,   EGF↓, 2,   FGFR1↓, 1,   mitResp↓, 1,   MMP↓, 10,   mtDam↑, 1,   Raf↓, 2,   XIAP↓, 3,  

Core Metabolism/Glycolysis ⓘ

12LOX↓, 1,   AMPK↑, 2,   CAIX↑, 1,   cMyc↓, 9,   p‑cMyc↑, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   HK2↓, 3,   lactateProd↓, 1,   LDH↑, 1,   LDHA↓, 2,   NADPH↑, 1,   PDK1↓, 2,   PDK3↑, 1,   PFK↓, 1,   PI3K/Akt↓, 1,   PI3k/Akt/mTOR↓, 1,   PKM2↓, 2,   PPARγ↑, 1,   p‑S6↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 18,   p‑Akt↓, 7,   APAF1↑, 2,   Apoptosis↓, 1,   Apoptosis↑, 23,   BAD↓, 1,   Bak↑, 1,   BAX↓, 2,   BAX↑, 19,   Bax:Bcl2↑, 3,   Bcl-2↓, 21,   Bcl-xL↓, 7,   BID↑, 1,   BIM↑, 1,   Casp↑, 1,   Casp12↑, 1,   Casp3↓, 3,   Casp3↑, 17,   cl‑Casp3↑, 6,   proCasp3↓, 1,   Casp7↑, 3,   Casp8↑, 7,   cl‑Casp8↑, 3,   proCasp8↓, 1,   Casp9↑, 18,   cl‑Casp9↑, 3,   proCasp9↓, 2,   cFLIP↓, 1,   Chk2↓, 1,   Chk2↑, 2,   Cyt‑c↑, 12,   Diablo↑, 1,   DR5↓, 1,   DR5↑, 4,   FADD↑, 1,   Fas↑, 4,   FasL↑, 3,   HEY1↓, 1,   hTERT/TERT↓, 3,   IAP1↓, 1,   iNOS↓, 1,   JNK↓, 1,   JNK↑, 3,   p‑JNK↓, 1,   MAPK↓, 5,   MAPK↑, 4,   Mcl-1↓, 5,   MDM2↓, 7,   NAIP↓, 1,   NICD↓, 1,   p27↑, 10,   p38↑, 4,   p‑p38↓, 1,   p‑p38↑, 1,   PUMA↑, 2,   survivin↓, 8,   Telomerase↓, 1,   TRAIL↑, 1,   TumCD↑, 3,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 2,   p‑HER2/EBBR2↓, 1,   Sp1/3/4↓, 2,  

Transcription & Epigenetics ⓘ

p‑cJun↑, 1,   EZH2↓, 1,   H3↓, 2,   H3↑, 1,   ac‑H3↑, 1,   miR-21↓, 1,   miR-21↑, 1,   other↓, 1,   pRB↓, 1,   p‑pRB↓, 1,   tumCV↓, 6,  

Protein Folding & ER Stress ⓘ

CHOP↑, 7,   eIF2α↑, 2,   p‑eIF2α↑, 2,   ER Stress↓, 1,   ER Stress↑, 9,   GRP78/BiP↑, 4,   HSP70/HSPA5↓, 3,   HSP90↓, 4,   PERK↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 2,   BNIP3↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3B-II↑, 2,   LC3II↑, 1,   p62↑, 1,   TumAuto↑, 4,  

DNA Damage & Repair ⓘ

ATM↑, 1,   CHK1↓, 2,   CHK1↑, 1,   DNAdam↑, 6,   DNArepair↑, 1,   P53↑, 25,   PARP↓, 2,   PARP↑, 3,   cl‑PARP↑, 9,   PCNA↓, 6,   PCNA↝, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 19,   p‑CDK1↓, 1,   CDK2↓, 16,   CDK2↑, 1,   CDK4↓, 15,   Cyc↓, 1,   cycA1/CCNA1↓, 11,   cycA1/CCNA1↑, 2,   CycB/CCNB1↓, 50,   cycD1/CCND1↓, 13,   CycD3↓, 1,   cycE/CCNE↓, 5,   cycE1↓, 1,   E2Fs↓, 1,   P21↑, 28,   RB1↓, 1,   RB1↑, 1,   p‑RB1↓, 2,   TumCCA↓, 1,   TumCCA↑, 39,  

Proliferation, Differentiation & Cell State ⓘ

BMI1↓, 1,   CD44↓, 1,   cDC2↓, 5,   cFos↓, 1,   cMET↓, 1,   CSCs↓, 6,   EMT↓, 11,   EMT↑, 1,   EP4↑, 1,   ERK↓, 6,   ERK↑, 2,   p‑ERK↓, 3,   FGF↓, 1,   FOXO3↓, 1,   FOXO3↑, 1,   p‑FOXO3↓, 1,   Gli1↓, 1,   GSK‐3β↓, 3,   GSK‐3β↑, 2,   p‑GSK‐3β↓, 1,   H3K27ac↓, 1,   HDAC↓, 2,   HDAC10↓, 1,   HH↓, 1,   IGF-1↓, 1,   IGF-1R↓, 1,   IGFBP3↑, 1,   mTOR↓, 11,   p‑mTOR↓, 1,   mTORC2↓, 1,   Nanog↓, 3,   NOTCH↓, 3,   NOTCH1↓, 2,   NOTCH1↑, 1,   OCT4↓, 2,   P70S6K↓, 1,   p‑P70S6K↓, 1,   p‑P90RSK↑, 1,   PI3K↓, 14,   p‑PI3K↓, 1,   PTEN↓, 1,   PTEN↑, 1,   RAS↓, 4,   Shh↓, 3,   Smo↓, 1,   SOX2↓, 2,   STAT3↓, 10,   p‑STAT3↓, 1,   TAZ↓, 1,   TOP1↓, 1,   TOP2↓, 3,   TumCG↓, 7,   TumCG↑, 1,   Wnt↓, 3,   Wnt/(β-catenin)↓, 2,  

Migration ⓘ

5LO↓, 1,   AEG1↓, 1,   AP-1↓, 2,   Ca+2↑, 2,   i-Ca+2↑, 1,   Cdc42↑, 1,   CLDN2↓, 1,   E-cadherin↑, 8,   E-cadherin↝, 1,   ER-α36↓, 1,   FAK↓, 3,   p‑FAK↓, 2,   Ki-67↓, 2,   KRAS↓, 1,   MMP1↓, 1,   MMP13↓, 2,   MMP2↓, 13,   MMP3↓, 1,   MMP7↓, 1,   MMP9↓, 13,   MMP9↑, 2,   MMPs↓, 4,   N-cadherin↓, 6,   N-cadherin↝, 1,   PDGF↓, 2,   PKCδ↓, 3,   Rho↓, 2,   ROCK1↓, 3,   Slug↓, 3,   Snail↓, 5,   TGF-β↓, 3,   TIMP1↑, 1,   TIMP2↑, 2,   Treg lymp↓, 1,   TSP-1↑, 1,   TumCI↓, 5,   TumCMig↓, 5,   TumCP↓, 21,   TumCP↑, 1,   TumMeta↓, 6,   TumMeta↑, 1,   Twist↓, 3,   uPA↓, 5,   uPAR↓, 1,   VCAM-1↓, 1,   Vim↓, 8,   Zeb1↓, 1,   α-tubulin↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 9,   ATF4↑, 3,   EGFR↓, 3,   p‑EGFR↓, 1,   Hif1a↓, 7,   LOX1↓, 1,   NO↓, 1,   NO↑, 1,   PDGFR-BB↓, 1,   VEGF↓, 14,   VEGFR2↓, 4,  

Barriers & Transport ⓘ

BBB↑, 2,   GLUT1↓, 2,   GLUT1↑, 1,   GLUT3↑, 1,   P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

CD4+↓, 1,   CD4+↑, 1,   COX2↓, 11,   COX2↑, 1,   CRP↓, 1,   CXCR4↓, 3,   FOXP3↓, 1,   IFN-γ↓, 1,   Igs↑, 1,   IKKα↓, 3,   p‑IKKα↓, 1,   IL1↓, 2,   IL10↓, 1,   IL12↓, 1,   IL1α↓, 1,   IL1β↓, 5,   IL2↓, 1,   IL2↑, 1,   IL6↓, 9,   IL8↓, 4,   Inflam↓, 2,   JAK1↓, 1,   JAK2↓, 1,   MCP1↓, 1,   NF-kB↓, 15,   p‑NF-kB↑, 1,   NK cell↑, 2,   p50↓, 1,   PD-L1↓, 2,   PGE2↓, 2,   PSA↓, 1,   T-Cell↑, 1,   Th1 response↑, 1,   TLR4↓, 2,   TNF-α↓, 7,   TNF-α↑, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,   CDK6↓, 2,   ER(estro)↓, 1,   RANKL↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 6,   BioAv↑, 3,   BioAv↝, 1,   ChemoSen↓, 1,   ChemoSen↑, 12,   Dose?, 1,   Dose↝, 2,   Dose∅, 1,   eff↓, 10,   eff↑, 20,   eff↝, 2,   Half-Life↓, 2,   MDR1↓, 1,   RadioS↑, 6,   selectivity↑, 7,  

Clinical Biomarkers ⓘ

AR↓, 2,   CRP↓, 1,   E6↓, 1,   E7↓, 1,   EGFR↓, 3,   p‑EGFR↓, 1,   EZH2↓, 1,   GutMicro↑, 1,   HER2/EBBR2↓, 2,   p‑HER2/EBBR2↓, 1,   hTERT/TERT↓, 3,   IL6↓, 9,   Ki-67↓, 2,   KRAS↓, 1,   LDH↑, 1,   PD-L1↓, 2,   PSA↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 5,   AntiTum↑, 1,   cardioP↑, 2,   chemoP↑, 2,   ChemoSideEff↓, 1,   OS↑, 1,   radioP↑, 2,   RenoP↑, 2,   toxicity↓, 2,   TumVol↓, 2,   TumW↓, 2,  
Total Targets: 393

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 8,   Catalase↑, 5,   GPx↑, 3,   GSH↑, 5,   GSR↑, 1,   GSTs↑, 2,   HO-1↑, 1,   Keap1↓, 1,   lipid-P↓, 4,   MDA↓, 3,   MPO↓, 1,   Nrf1↑, 1,   NRF2↑, 4,   Prx↑, 1,   ROS↓, 10,   SOD↑, 5,   SOD2↑, 1,   TBARS↓, 1,  

Metal & Cofactor Biology ⓘ

IronCh↓, 1,   IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   FASN↓, 1,   H2S↑, 1,   LDH↓, 2,  

Cell Death ⓘ

Akt↓, 1,   Casp3?, 1,   cl‑Casp8↑, 1,   iNOS↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 1,  

DNA Damage & Repair ⓘ

PARP↑, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,   PI3K↓, 1,  

Migration ⓘ

AntiAg↑, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   NO↓, 2,  

Barriers & Transport ⓘ

BBB↑, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IL10↓, 1,   IL17↓, 1,   IL1β↓, 1,   IL6↓, 2,   IL8↓, 1,   Inflam↓, 6,   MCP1↓, 1,   NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 4,   BioAv↑, 1,   eff↑, 1,   Half-Life↑, 1,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   BP↓, 2,   creat↓, 1,   GutMicro↑, 1,   IL6↓, 2,   LDH↓, 2,  

Functional Outcomes ⓘ

cardioP↑, 3,   cognitive↑, 1,   hepatoP↑, 4,   memory↑, 1,   neuroP↑, 5,   Pain↓, 1,   toxicity↓, 2,  
Total Targets: 71

Scientific Paper Hit Count for: CycB/CCNB1, Cyclin B
8 Quercetin
4 Propolis -bee glue
3 Apigenin (mainly Parsley)
3 Plumbagin
2 Allicin (mainly Garlic)
2 Baicalein
2 Betulinic acid
2 Chrysin
2 Curcumin
2 Luteolin
2 Magnolol
2 Silymarin (Milk Thistle) silibinin
1 Andrographis
1 Artemisinin
1 Ashwagandha(Withaferin A)
1 Astaxanthin
1 Aloe anthraquinones
1 Berberine
1 Biochanin A
1 Bufalin/Huachansu
1 Emodin
1 Garcinol
1 Laetrile B17 Amygdalin
1 Lycopene
1 Melatonin
1 Magnetic Fields
1 Phenylbutyrate
1 Piperlongumine
1 Resveratrol
1 Sulforaphane (mainly Broccoli)
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:379  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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