cycD1/CCND1 Cancer Research Results

cycD1/CCND1, cyclin D1 pathway: Click to Expand ⟱
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Also called CCND1 Gatekeeper of Cell-Cycle Commitment
The main function of cyclin D1 is to maintain cell cycle and to promote cell proliferation. Cyclin D1 is a key regulatory protein involved in the cell cycle, particularly in the transition from the G1 phase to the S phase. It is part of the cyclin-dependent kinase (CDK) complex, where it binds to CDK4 or CDK6 to promote cell cycle progression.
Cyclin D1 is crucial for the regulation of the cell cycle. Overexpression or dysregulation of cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.
Cyclin D1 is often found to be overexpressed in various cancers.
Cyclin D1 can interact with tumor suppressor proteins, such as retinoblastoma (Rb). When cyclin D1 is overexpressed, it can lead to the phosphorylation and inactivation of Rb, releasing E2F transcription factors that promote the expression of genes required for DNA synthesis and cell cycle progression.
Cyclin D1 is influenced by various signaling pathways, including the PI3K/Akt and MAPK pathways, which are often activated in cancer.
In some cancers, high levels of cyclin D1 expression have been associated with poor prognosis, making it a potential biomarker for cancer progression and treatment response.
Scientific Papers found: Click to Expand⟱
2423- 2DG,  SRF,    2-Deoxyglucose and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells
- in-vitro, HCC, NA
ChemoSen↑, 2DG and sorafenib in combination suppressed the proliferation and motility of HCC cells more effectively than 2DG or sorafenib alone,
TumCP↓, In the present study, 3 µM 2DG and 30 µM sorafenib significantly suppressed the proliferation of HLF and HCC PLC/PRF/5 cells.
cycD1/CCND1↓, Sorafenib and 2DG independently decrease cyclin D1 expression
MMP9↓, expression of MMP9 significantly decreased when cells were treated with a combination of 2DG and sorafenib compared with 2DG or sorafenib alone

1334- AG,    Astragalus membranaceus: A Review of Its Antitumor Effects on Non-Small Cell Lung Cancer
- Review, NA, NA
TumCP↓,
Apoptosis↑,
NF-kB↓,
p50↓,
cycD1/CCND1↓,
Bcl-xL↓,
ChemoSen↑, AS-IV can enhance paclitaxel-induced cell apoptosis and cell cycle arrest at G2/M phase
angioG↓,
ChemoSen↑, Enhances Sensitivity to Cisplatin

5434- AG,    Recent Advances in the Mechanisms and Applications of Astragalus Polysaccharides in Liver Cancer Treatment: An Overview
- Review, Liver, NA
AntiCan↑, Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including the promotion of apoptosis, inhibition of proliferation, suppression of epithelial–mesenchymal transition, regulation of
Apoptosis↑,
TumCP↓,
EMT↓,
Imm↑, improving host immune response
ChemoSen↑, APS exhibits synergistic effects when combined with conventional chemotherapeutics and interventional treatments such as transarterial chemoembolisation, improving efficacy and reducing toxicity.
BioAv↓, limitations such as low bioavailability and a lack of large-scale clinical trials remain challenges for clinical translation.
TumCG↓, APS significantly inhibited tumour growth in H22-bearing mice with a dose-dependent effect (100, 200, 400 mg/kg), with the 400 mg/kg group achieving a tumour inhibition rate of 59.01%
IL2↑, APS enhance the thymus and spleen indices and elevates the key cytokines, including IL-2, IL-12, and TNF-α.
IL12↑,
TNF-α↑,
P-gp↓, APS reversed chemoresistance by downregulating P-glycoprotein and MDR1 mRNA expression
MDR1↓,
QoL↑, These effects contributed to improved treatment tolerance and enhanced quality of life [39].
Casp↑, APS can activate both the intrinsic and extrinsic apoptotic pathways, leading to caspase activation and DNA fragmentation
DNAdam↑,
Bcl-2↓, Mechanistically, APS downregulate antiapoptotic proteins such as Bcl-2 while upregulating proapoptotic proteins such as Bax and cleaved caspase-3.
BAX↑,
MMP↓, APS have been shown to disrupt the mitochondrial membrane potential and promote the release of cytochrome c, thereby enhancing apoptotic cascades in hepatocellular carcinoma models.
Cyt‑c↑,
NOTCH1↓, APS (0.1, 0.5, and 1.0 mg/mL) were shown to reduce both mRNA and protein levels of Notch1 in a concentration-dependent manner.
GSK‐3β↓, APS significantly inhibited the proliferation of HepG2 cells by downregulating the expression of glycogen synthase kinase-3β (GSK-3β), with 200 μg/mL being the most effective concentration.
TumCCA↑, APS exerted these effects by inducing cell cycle arrest at the G2/M and S phases, thereby impeding tumour cell proliferation [35].
GSH↓, HepG2 cells. APS also reduced intracellular glutathione (GSH) levels, increased reactive oxygen species (ROS) and lipid peroxidation levels, and elevated intracellular iron ion concentrations—all in a dose-dependent manner.
ROS↑,
lipid-P↑,
c-Iron↑,
GPx4↓, APS treatment led to the downregulation of GPX4 and upregulation of ACSL4, indicating that APS promotes ferroptosis in liver cancer cells.
ACSL4↑,
Ferroptosis↑,
Wnt↓, inhibit the expression of key proteins involved in the Wnt/β-catenin signalling pathway
β-catenin/ZEB1↓,
cycD1/CCND1↓, by downregulating the key oncogenic targets, including β-catenin, C-myc, and cyclin D1, which subsequently reduces Bcl-2 expression and activates the apoptotic cascade in HepG2 liver cancer cells.
Akt↓, It also inhibited the Akt/p-Akt signalling pathway.
PI3K↓, APS inhibit the PI3K/AKT/mTOR signalling pathway, which is a central negative regulator of autophagy.
mTOR↓,
CXCR4↓, PS upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker vimentin and the chemokine receptor CXCR4 at both mRNA and protein levels, suggesting that APS suppress liver cancer cell growth and metastasis by inhibiting
Vim↓,
PD-L1↓, APS interfere with immune checkpoint signalling by downregulating Programmed death-ligand 1 (PD-L1) expression on tumour cells.
eff↑, The preparation of polysaccharide–SeNP composites typically involves using sodium selenite (Na2SeO3) as the precursor and ascorbic acid (Vc) as the reducing agent, with synthesis carried out via a chemical reduction method in a polysaccharide solutio
eff↑, Mechanistic investigations revealed that AASP–SeNPs elevated intracellular ROS levels and reduced the mitochondrial membrane potential (∆Ψm).
ChemoSen↑, APS enhance doxorubicin-induced endoplasmic reticulum (ER) stress by reducing O-GlcNAcylation levels, thereby promoting apoptosis of liver cancer cells.
ChemoSen↑, APS inhibited BEL-7404 human liver cancer cell growth in a concentration-dependent manner and showed stronger cytotoxicity when combined with cisplatin.
chemoP↑, APS protects against chemotherapy-induced liver injury, particularly that caused by CTX, through antiapoptotic mechanisms

4417- AgNPs,    Caffeine-boosted silver nanoparticles target breast cancer cells by triggering oxidative stress, inflammation, and apoptotic pathways
- in-vitro, BC, MDA-MB-231
ROS↑, Caf-AgNPs significantly increased ROS, malondialdehyde, COX-2, IL-1β, and TNF-α level in BC cells, which was accompanied by a decrease in glutathione levels.
MDA↑,
COX2↑,
IL1β↑,
TNF-α↑,
GSH↓,
Cyt‑c↑, increased levels of cytosolic cytochrome c, caspase-3, and Bax proteins, as well as a significant decrease in Bcl-2 expression and Bcl-2/Bax ratio
Casp3↑,
BAX↑,
Bcl-2↓,
LDH↓, Cancer cells subjected to Caf-AgNPs demonstrated elevated lactate dehydrogenase (LDH) membrane leakage
cycD1/CCND1↓, notable downregulation of cyclin D1 and cyclin-dependent kinase 2 (CDK2) mRNA expression
CDK2↓,
TumCCA↑, several mechanisms for cellular destruction, including cell cycle arrest, oxidative stress induction, modulation of the inflammatory response, and mitochondrial apoptosis
mt-Apoptosis↑,

4409- AgNPs,    Plant-based synthesis of gold and silver nanoparticles using Artocarpus heterophyllus aqueous leaf extract and its anticancer activities
- in-vitro, BC, MCF-7
tumCV↓, , AuNPs had no anticancer activity. In contrast, AgNPs showed potent anticancer effects, with inhibitory concentration (IC50) values of 124.626 and 54.981 µg/mL at 48 and 72 hours, respectively.
TumCCA↑, The AgNPs treatment increased the proportion of cells in G2/M phase, indicating the induction of mitotic catastrophe leading to cell death
cycD1/CCND1↓, AgNPs downregulated the expression of several oncogenes associated with cancer cell proliferation and survival (cyclin D1, COX-2, HER-2, and miR622
COX2↓,
HER2/EBBR2↓,

4584- AgNPs,    Silver Nanoparticles Synthesized Using Carica papaya Leaf Extract (AgNPs-PLE) Causes Cell Cycle Arrest and Apoptosis in Human Prostate (DU145) Cancer Cells
- in-vitro, Pca, DU145
selectivity↑, AgNPs-PLE when compared with AgNPs-citric acid or PLE showed better efficacy against cancer cells and was also relatively less toxic to normal cells.
ROS↑, ROS production was observed at earlier time points in presence of AgNPs-PLE, suggesting its role behind apoptosis in DU145 cells.
BAX↑, induction of Bax, cleaved caspase-3, and cleaved PARP proteins. G1-S phase cell cycle check point marker, cyclin D1 was down-regulated along with an increase in cip1/p21 and kip1/p27 tumor suppressor proteins by AgNPs-PLE.
cl‑Casp3↑,
p‑PARP↑,
TumCCA↑,
cycD1/CCND1↓,
p27↑,
P21↑,
AntiCan↑, These findings suggest the anti-cancer properties of AgNPs-PLE.

358- AgNPs,    Preparation of triangular silver nanoparticles and their biological effects in the treatment of ovarian cancer
- vitro+vivo, Ovarian, SKOV3
TumCCA↑, arrested the cell cycle in G0/G1 phase
ROS↑,
Casp3↑,
TumCG↓,
cycD1/CCND1↓, and cyclinA2

382- AgNPs,    Investigation the apoptotic effect of silver nanoparticles (Ag-NPs) on MDA-MB 231 breast cancer epithelial cells via signaling pathways
- in-vitro, BC, MDA-MB-231
Apoptosis↑,
BAX↑,
Bcl-2↓,
P53↑,
PTEN↑,
hTERT/TERT↓,
p‑ERK↓, p-ERK/Total ERK
cycD1/CCND1↓,

5356- AL,    Therapeutic role of allicin in gastrointestinal cancers: mechanisms and safety aspects
- Review, GC, NA
Apoptosis↑, induction of apoptosis, inhibition of proliferation, and disruption of cancer cell signaling pathways, including the MAPK, PI3K/AKT, and NF-κB pathways.
TumCP↓,
MAPK↓,
PI3K↓,
Akt↓,
NF-kB↓,
AntiCan↑, Allicin and its other derivatives, such as diallyl disulfide (DADS) and ajoene, have been found to have strong anticancer potential both in vitro and in vivo.
ChemoSen↑, effectiveness of allicin in augmenting conventional chemotherapy and retarding tumor growth proves that allicin is one of the most efficient complementary therapies.
TumCCA↑, In liver cancer, allicin has been shown to mediate cell cycle arrest and apoptosis
Apoptosis↑,
BioAv↑, Allicin (diallyl thiosulfinate) is a compound that is generated when a garlic clove is crushed
selectivity↑, Furthermore, it has no influence on the growth of healthy intestinal cells when it causes stomach cancer cells to undergo apoptosis
TGF-β↓, Allicin can reduce the production of TGF-β2 and its receptor after directly entering gastric cancer cells.
ROS↑, It induces oxidative stress by generating reactive oxygen species (ROS), leading to DNA damage and activation of key apoptotic mediators such as phospho-p53 and p21 [81].
DNAdam↑,
p‑P53↑,
P21↑,
cycD1/CCND1↓, Additionally, cyclin D1, cyclin E, and cyclin-dependent kinases (CDKs) can all be inhibited by allicin.
cycE/CCNE↓,
CDK4↓, suppressing the CDK-4/6/cyclin D complex
CDK6↓,
MMP↓, By lowering the outer mitochondrial membrane potential (MMP), allicin raises levels of nuclear factor kappa B (NF-κB), the proapoptotic protein Bax, while decreasing the antiapoptotic protein Bcl-2, which leads to apoptosis.
NF-kB↑,
BAX↑,
Bcl-2↓,
ER Stress↑, cellular effects of allicin, including its role in inducing ER stress
Casp↑, enhancing caspase activation and apoptosis-inducing factor (AIF)-mediated cell death.
AIF↑,
Fas↑, increasing Fas receptor expression and its binding to Fas ligand (FasL), leading to apoptosis through caspase-8 and cytochrome c activation.
Casp8↑,
Cyt‑c↑,
cl‑PARP↑, leading to poly (ADP-ribose) polymerase (PARP) cleavage and DNA fragmentation.
Ca+2↑, allicin elevates intracellular free Ca2⁺ levels, causing endoplasmic reticulum (ER) stress, which plays a critical role in apoptosis induction
*NRF2↑, by activating the Nrf2 pathway via KLF9, allicin protects against arsenic trioxide-induced liver damage,
*chemoP↑, Additionally, allicin has shown promise in reducing hepatotoxicity caused by tamoxifen (TAM), a commonly used treatment for hormone-dependent breast cancer
*GutMicro↑, Shi et al. [85] found that allicin can ameliorate high-fat diet-induced obesity in mice by altering their gut microbiome.
CycB/CCNB1↑, DATS impaired cell survival in the G2 phase by significantly upregulating cyclins A2 and B1.
H2S↑, DATS can also react with the cellular thiol glutathione to create H2S gas, which can control several other cellular functions [79].
HIF-1↓, allicin treatment (40 µg/ml) for NSCLC lowers the expression of HIF-1 and HIF-2 in hypoxic cells [73]
RadioS↑, Allicin has been shown to increase the sensitivity of X-ray radiation therapy in colorectal cancer, presumably by suppressing the levels of NF-κB, IKKβ mRNA, p-NF-κB, and p-IKKβ protein expression in vitro and in vivo

2655- AL,    Allicin and Digestive System Cancers: From Chemical Structure to Its Therapeutic Opportunities
- Review, GC, NA
TGF-β↓, Allicin can reduce the expression of TGF-2 and its receptor after entering directly into gastric cancer cell
cycD1/CCND1↓, followed by not only downexpression of cyclinD1, cyclinE, and cyclin-dependent kinase (CDK),
cycE/CCNE↓,
CDK1↓, cyclin-dependent kinase (CDK)
DNAdam↑, but also causing DNA damage and generating ROS
ROS↑,
BAX↑, Allicin increases the levels of Bax (proapoptotic protein), Bcl-2 (antiapoptotic protein), and JNK
JNK↑,
MMP↓, through reduction in outer mitochondrial membrane potential
p38↑, allicin induces p38 mitogen that could induce the protein kinase (MAPK) and then increase the expression of Fas binding to Fas ligand (Fas L) and finally activate death pathway through activation of cyt C and caspase-8.
MAPK↑,
Fas↑,
Cyt‑c↑,
Casp8↑,
PARP↑, allicin makes caspase-dependent apoptosis through elevating PARP, caspase-3 and caspase-9, which are mediated by enhanced discharging of mitochondria cyt C to the cytosol.
Casp3↑,
Casp9↑,
Ca+2↑, allicin induces apoptosis via increasing the amounts of free Ca2+, ER stress.
ER Stress↑,
P21↑, generating ROS to produce p21 and phospho-p53 (Ser15).
CDK2↓, Then p21 suppressed the CDK-4/6/cyclinD complex, P21-PCNA, P21-CDK2, and subsequently reduced cdk1/cyclinB1 complex for G2/M phase cell cycle arrest
CDK6↑,
TumCCA↑,
CDK4↓, Then p21 suppressed the CDK-4/6/cyclinD complex

276- ALA,    Alpha lipoic acid diminishes migration and invasion in hepatocellular carcinoma cells through an AMPK-p53 axis
- in-vitro, HCC, HepG2 - in-vitro, HCC, Hep3B
P53↑,
EMT↓,
AMPK↑,
cycD1/CCND1↓,
TumCMig↓, only in HCC cells that express wild type p53

1158- And,  GEM,    Andrographolide causes apoptosis via inactivation of STAT3 and Akt and potentiates antitumor activity of gemcitabine in pancreatic cancer
TumCP↓,
TumCCA↑,
Apoptosis↑,
STAT3↓,
Akt↓,
P21↑,
BAX↑,
cycD1/CCND1↓,
cycE/CCNE↓,
survivin↓,
XIAP↓,
Bcl-2↓,
eff↑, ANDRO combined with gemcitabine significantly induce stronger cell cycle arrest and more obvious apoptosis than each single treatment.

2639- Api,    Plant flavone apigenin: An emerging anticancer agent
- Review, Var, NA
*antiOx↑, Apigenin (4′, 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties
*Inflam↓,
AntiCan↑,
ChemoSen↑, Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers.
BioEnh↑, Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies.
chemoPv↑, apigenin highlighting its potential activity as a chemopreventive and therapeutic agent.
IL6↓, In taxol-resistant ovarian cancer cells, apigenin caused down regulation of TAM family of tyrosine kinase receptors and also caused inhibition of IL-6/STAT3 axis, thereby attenuating proliferation.
STAT3↓,
NF-kB↓, apigenin treatment effectively inhibited NF-κB activation, scavenged free radicals, and stimulated MUC-2 secretion
IL8↓, interleukin (IL)-6, and IL-8
eff↝, The anti-proliferative effects of apigenin was significantly higher in breast cancer cells over-expressing HER2/neu but was much less efficacious in restricting the growth of cell lines expressing HER2/neu at basal levels
Akt↓, Apigenin interferes in the cell survival pathway by inhibiting Akt function by directly blocking PI3K activity
PI3K↓,
HER2/EBBR2↓, apigenin administration led to the depletion of HER2/neu protein in vivo
cycD1/CCND1↓, Apigenin treatment in breast cancer cells also results in decreased expression of cyclin D1, D3, and cdk4 and increased quantities of p27 protein
CycD3↓,
p27↑,
FOXO3↑, In triple-negative breast cancer cells, apigenin induces apoptosis by inhibiting the PI3K/Akt pathway thereby increasing FOXO3a expression
STAT3↓, In addition, apigenin also down-regulated STAT3 target genes MMP-2, MMP-9, VEGF and Twist1, which are involved in cell migration and invasion of breast cancer cells [
MMP2↓,
MMP9↓,
VEGF↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
Twist↓,
MMP↓, Apigenin treatment of HGC-27 and SGC-7901 gastric cancer cells resulted in the inhibition of proliferation followed by mitochondrial depolarization resulting in apoptosis
ROS↑, Further studies revealed apigenin-induced apoptosis in hepatoma tumor cells by utilizing ROS generated through the activation of the NADPH oxidase
NADPH↑,
NRF2↓, Apigenin significantly sensitized doxorubicin-resistant BEL-7402 (BEL-7402/ADM) cells to doxorubicin (ADM) and increased the intracellular concentration of ADM by reducing Nrf2-
SOD↓, In human cervical epithelial carcinoma HeLa cells combination of apigenin and paclitaxel significantly increased inhibition of cell proliferation, suppressing the activity of SOD, inducing ROS accumulation leading to apoptosis by activation of caspas
COX2↓, melanoma skin cancer model where apigenin inhibited COX-2 that promotes proliferation and tumorigenesis
p38↑, Additionally, it was shown that apigenin treatment in a late phase involves the activation of p38 and PKCδ to modulate Hsp27, thus leading to apoptosis
Telomerase↓, apigenin inhibits cell growth and diminishes telomerase activity in human-derived leukemia cells
HDAC↓, demonstrated the role of apigenin as a histone deacetylase inhibitor. As such, apigenin acts on HDAC1 and HDAC3
HDAC1↓,
HDAC3↓,
Hif1a↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
angioG↓, Moreover, apigenin was found to inhibit angiogenesis, as suggested by decreased HIF-1α and VEGF expression in cancer cells
uPA↓, Furthermore, apigenin intake resulted in marked inhibition of p-Akt, p-ERK1/2, VEGF, uPA, MMP-2 and MMP-9, corresponding with tumor growth and metastasis inhibition in TRAMP mice
Ca+2↑, Neuroblastoma SH-SY5Y cells treated with apigenin led to induction of apoptosis, accompanied by higher levels of intracellular free [Ca(2+)] and shift in Bax:Bcl-2 ratio in favor of apoptosis, cytochrome c release, followed by activation casp-9, 12
Bax:Bcl2↑,
Cyt‑c↑,
Casp9↑,
Casp12↑,
Casp3↑, Apigenin also augmented caspase-3 activity and PARP cleavage
cl‑PARP↑,
E-cadherin↑, Apigenin treatment resulted in higher levels of E-cadherin and reduced levels of nuclear β-catenin, c-Myc, and cyclin D1 in the prostates of TRAMP mice.
β-catenin/ZEB1↓,
cMyc↓,
CDK4↓, apigenin exposure led to decreased levels of cell cycle regulatory proteins including cyclin D1, D2 and E and their regulatory partners CDK2, 4, and 6
CDK2↓,
CDK6↓,
IGF-1↓, A reduction in the IGF-1 and increase in IGFBP-3 levels in the serum and the dorsolateral prostate was observed in apigenin-treated mice.
CK2↓, benefits of apigenin as a CK2 inhibitor in the treatment of human cervical cancer by targeting cancer stem cells
CSCs↓,
FAK↓, Apigenin inhibited the tobacco-derived carcinogen-mediated cell proliferation and migration involving the β-AR and its downstream signals FAK and ERK activation
Gli↓, Apigenin inhibited the self-renewal capacity of SKOV3 sphere-forming cells (SFC) by downregulating Gli1 regulated by CK2α
GLUT1↓, Apigenin induces apoptosis and slows cell growth through metabolic and oxidative stress as a consequence of the down-regulation of glucose transporter 1 (GLUT1).

314- Api,    Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis
- in-vitro, SCC, HaCaT - in-vitro, SCC, SCC25
TumCCA↑, G2/M cell cycle arrest.
cycD1/CCND1↓,
cycE/CCNE↓,
CDK1/2/5/9∅, CDK1

207- Api,    Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells
- in-vitro, Pca, LNCaP
PSA↓,
cycD1/CCND1↓, cyclinD1 and cyclinD2
cycE/CCNE↓,
CDK2↓,
CDK4/6↓,
P21↑,
AR↓,

211- Api,    Suppression of NF-κB and NF-κB-Regulated Gene Expression by Apigenin through IκBα and IKK Pathway in TRAMP Mice
- in-vivo, Pca, NA
IKKα↓,
NF-kB↓,
cycD1/CCND1↓,
COX2↓,
Bcl-2↓,
Bcl-xL↓,
VEGF↓,
PCNA↓,
BAX↑,

3382- ART/DHA,    Repurposing Artemisinin and its Derivatives as Anticancer Drugs: A Chance or Challenge?
- Review, Var, NA
AntiCan↑, antimalarial drug, artemisinin that has shown anticancer activities in vitro and in vivo.
toxicity↑, safety of artemisinins in long-term cancer therapy requires further investigation.
Ferroptosis↑, Artemisinins acts against cancer cells via various pathways such as inducing apoptosis (Zhu et al., 2014; Zuo et al., 2014) and ferroptosis via the generation of reactive oxygen species (ROS) (Zhu et al., 2021) and causing cell cycle arrest
ROS↑,
TumCCA↑,
BioAv↝, absolute bioavailability was estimated to be 21.6%. ART has good solubility and is not lipophilic
eff↝, ART would not distribute well to the tissues and might be more effective in treating cancers such as leukemia, hepatocellular carcinoma (HCC), or renal cell carcinoma because the liver and kidney are highly perfused organs.
Half-Life↓, Pharmacokinetic studies showed a relatively short t1/2 of artemisinins. For ART, t1/2 was 0.41 h
Ferritin↓, Figure 3
GPx4↓,
NADPH↓,
GSH↓,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
VEGF↓, angiogenesis
IL8↓,
COX2↓,
MMP9↓,
E-cadherin↑,
MMP2↓,
NF-kB↓,
p16↑, cell cycle arrest
CDK4↓,
cycD1/CCND1↓,
p62↓, autophagy
LC3II↑,
EMT↓, suppressing EMT and CSCs
CSCs↓,
Wnt↓, Depress Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
uPA↓, Inhibit u-PA activity, protein and mRNA expression
TumAuto↑, Emerging evidence suggests that autophagy induction is one of the molecular mechanisms underlying anticancer activity of artemisinins
angioG↓, Inhibition of Angiogenesis
ChemoSen↑, Many studies also reported that the use of artemisinins sensitized cancer cells to conventional chemotherapy and exerted a synergistic effect on apoptosis, inhibition of cell growth, and a reduction of cell viability, leading to a lower IC50 value

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↑,

556- ART/DHA,    Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing
- Review, NA, NA
IL6↓,
IL1↓, IL-1β
TNF-α↓,
TGF-β↓, TGF-β1
NF-kB↓,
MIP2↓,
PGE2↓,
NO↓,
Hif1a↓,
KDR/FLK-1↓,
VEGF↓,
MMP2↓,
TIMP2↑,
ITGB1↑,
NCAM↑,
p‑ATM↑,
p‑ATR↑,
p‑CHK1↑,
p‑Chk2↑,
Wnt/(β-catenin)↓,
PI3K↓,
Akt↓,
ERK↓, ERK1/2
cMyc↓,
mTOR↓,
survivin↓,
cMET↓,
EGFR↓,
cycD1/CCND1↓,
cycE1↓,
CDK4/6↓,
p16↑,
p27↑,
Apoptosis↑,
TumAuto↑,
Ferroptosis↑,
oncosis↑,
TumCCA↑, G0/G1 into M phase, G0/G1 into S phase, G1 and G2/M
ROS↑, ovarian cancer cell line model, artesunate induced oxidative stress, DNA double-strand breaks (DSBs) and downregulation of RAD51 foci
DNAdam↑,
RAD51↓,
HR↓,

564- ART/DHA,  Cisplatin,    Dihydroartemisinin as a Putative STAT3 Inhibitor, Suppresses the Growth of Head and Neck Squamous Cell Carcinoma by Targeting Jak2/STAT3 Signaling
- in-vitro, NA, HN30
JAK2↓,
STAT3↓,
MMP2↓,
MMP9↓,
Mcl-1↓,
Bcl-xL↓,
cycD1/CCND1↓,
VEGF↓,
TumCCA↑, G1 cell cycle arrest in HNSCC
ChemoSen↑, DHA also synergized with cisplatin in tumor inhibition in HNSCC cells

2323- ART/DHA,    Dihydroartemisinin represses esophageal cancer glycolysis by down-regulating pyruvate kinase M2
- in-vitro, ESCC, Eca109 - in-vitro, ESCC, EC9706
PKM2↓, DHA treatment cells, PKM2 was down-regulated and lactate product and glucose uptake were inhibited.
lactateProd↓,
GlucoseCon↓,
cycD1/CCND1↓, DHA treatment resulted in the down-regulation of the expression of PKM2, cyclin D1, Bcl-2, matrix metalloproteinase-2 (MMP2), vascular endothelial growth factor A (VEGF-A) and the up-regulation of caspase 3, cleaved-PARP and Bax
Bcl-2↓,
MMP2↓,
VEGF↓,
Casp3↑,
cl‑PARP↑,
BAX↑,
DNAdam↑, The specific mechanism of DHA towards cancer cells include inducing DNA damage and repair (Li et al., 2008), oxidative stress response by reactive oxygen species
ROS↑,

5174- Ash,    Withaferin A is a potent inhibitor of angiogenesis
- in-vitro, Nor, HUVECs
Inflam↓, he medicinal plant Withania somnifera is widely researched for its anti-inflammatory, cardioactive and central nervous system effects.
*TumCP↓, Withaferin A inhibits cell proliferation in HUVECs (IC50 =12 nM) at doses that are significantly lower than those required for tumor cell lines through a process associated with inhibition of cyclin D1 expression.
cycD1/CCND1↓,
NF-kB↓, inhibition of NF-kappa B by withaferin A in HUVECs occurs by interference with the ubiquitin-mediated proteasome pathway
angioG↓, withaferin A is shown to exert potent anti-angiogenic activity in vivo at doses that are 500-fold lower than those previously reported to exert anti-tumor activity in vivo

4820- ASTX,    Astaxanthin suppresses the malignant behaviors of nasopharyngeal carcinoma cells by blocking PI3K/AKT and NF-κB pathways via miR-29a-3p
- in-vitro, NPC, NA
TumCP↓, C666-1 cell proliferation, invasion, and migration were significantly suppressed by astaxanthin while cell apoptosis and cell cycle arrest at G1 phase were effectively enhanced in the context of 10 mg/mL astaxanthin.
TumCI↓,
Apoptosis↑,
TumCCA↑,
cycD1/CCND1↓, inhibitory effect of astaxanthin on Cyclin D1 and Bcl-2 protein levels as well as the promoting impact of astaxanthin on p21 and Bax were also amplified in combination with LY294002 or PTL treatment.
Bcl-2↓,
P21↑,
BAX↑,
PI3K↓, Astaxanthin significantly suppresses NPC cell proliferation, cell cycle arrest, migration, invasion while promoting cell apoptosis by inactivating PI3K/AKT and NF-κB pathways.
Akt↓,
NF-kB↓,
miR-29b↑, Astaxanthin upregulates miR-29a-3p expression to inactivate the PI3K/AKT and NF-κB pathways

4809- ASTX,    Astaxanthin Inhibits Proliferation of Human Gastric Cancer Cell Lines by Interrupting Cell Cycle Progression
- in-vitro, GC, AGS - in-vitro, GC, MKN45
tumCV↓, The viability of each cancer cell line was suppressed by astaxanthin in a dose-dependent manner with significantly decreased proliferation in KATO-III and SNU-1 cells.
TumCP↓,
TumCCA↑, Astaxanthin inhibits proliferation by interrupting cell cycle progression in KATO-III and SNU-1 gastric cancer cells.
p‑ERK↓, This may be caused by the inhibition of the phosphorylation of ERK and the enhanced expression of p27kip-1.
p27↑,
cycD1/CCND1↓, Astaxanthin downregulates p-ERK level in tumor cells, inhibiting the cyclin D1/CDK4 complex
CDK4↓,

1520- Ba,    Baicalein Induces G2/M Cell Cycle Arrest Associated with ROS Generation and CHK2 Activation in Highly Invasive Human Ovarian Cancer Cells
- in-vitro, Ovarian, SKOV3 - in-vitro, Ovarian, TOV-21G
TumCG↓,
TumCCA↑, G2/M phase
ROS↑, Baicalein-induced G2/M phase arrest is associated with an increased reactive oxygen species (ROS) production, DNA damage, and CHK2 upregulation and activation
DNAdam↑,
Chk2↑,
Dose∅, produced significant ROS in a dose- and time-dependent manner in SKOV-3 cells
p‑γH2AX↑, baicalein treatment increased the phosphorylation of H2AX (γH2AX)
CDC25↓,
CHK1↓,
cycD1/CCND1↓,
eff↓, CHK2 inhibitor indeed reduced the extent of CHK2 phosphorylation (Figure 4A) and protected SKOV-3 cells from baicalein-mediated G2/M arrest (Fig
12LOX↓, the pro-oxidative effect of baicalein, a specific inhibitor of 12-LOX, on ovarian cancer cells may occur through inhibiting the activity of 12-LOX, thereby inducing the accumulation of hydroxyl radicals.

2474- Ba,    Anticancer properties of baicalein: a review
- Review, Var, NA - in-vitro, Nor, BV2
ROS⇅, Like other flavonoids, baicalein can be either anti-oxidant or pro-oxidant, depending on its metabolism and concentration.
ROS↑, It is reported that baicalein generated ROS, subsequently caused endoplasmic reticulum (ER) stress, activated Ca2+-dependent mitochondrial death pathway, finally triggered apoptosis
ER Stress↑,
Ca+2↑,
Apoptosis↑,
eff↑, Due to this, ROS production is a mechanism shared by all non-surgical therapeutic approaches for cancer, including chemotherapy, radiotherapy and photodynamic therapy
DR5↑, baicalein-induced ROS generation up-regulated DR5 expression and then activated the extrinsic apoptotic pathway in human prostate cancer cells
12LOX↓, Baicalein is known as a 12-LOX inhibitor.
Cyt‑c↑, It markedly induced the release of Cytochrome c from mitochondria into the cytosol and activated Caspase-9, Caspase-7, and Caspase-3, concomitant with cleavage of the Caspase-3 substrate poly(ADP-ribose) polymerase
Casp7↑,
Casp9↑,
Casp3↑,
cl‑PARP↑,
TumCCA↑, Baicalein induces G1/S arrest due to increased Cyclin E expression, a major factor in the regulation of the G1/S checkpoint of the cell cycle, accompanied by reduced levels of Cdk 4 and Cyclin D1 in human lung squamous carcinoma (CH27) cells
cycE/CCNE↑,
CDK4↓,
cycD1/CCND1↓,
VEGF↓, In ovarian cancer cells, baicalein effectively lowered the protein level of VEGF, c-Myc, HIF-α, and NFκB
cMyc↓,
Hif1a↓,
NF-kB↓,
BioEnh↑, curcumin and high-dose (−)-epicatechin were demonstrated to subsequently increase the absorption of baicalein
BioEnh↑, Baicalein can increase the oral bioavailability of tamoxifen by inhibiting cytochrome P450 (CYP) 3A4-mediated metabolism of tamoxifen in the small intestine and/or liver,
P450↓,
*Hif1a↓, In BV2 microglia, baicalein suppressed expression of hypoxia-induced HIF-1α and hypoxia responsive genes, including inducible nitric oxide synthase (iNOS), COX-2, and VEGF, by inhibiting ROS and PI3K/Akt pathway (Hwang et al. 2008).
*iNOS↓,
*COX2↓,
*VEGF↓,
*ROS↓,
*PI3K↓,
*Akt↓,

2626- Ba,    Molecular targets and therapeutic potential of baicalein: a review
- Review, Var, NA - Review, AD, NA - Review, Stroke, NA
AntiCan↓, anticancer, antidiabetic, antimicrobial, antiaging, neuroprotective, cardioprotective, respiratory protective, gastroprotective, hepatic protective, and renal protective effects
*neuroP↑,
*cardioP↑, Cardioprotective action of baicalein
*hepatoP↑,
*RenoP↑, baicalein’s capacity to lessen cisplatin-induced nephrotoxicity is probably due, at least in part, to the attenuation of renal oxidative and/or nitrative stress
TumCCA↑, Baicalein induces G1/S arrest in lung squamous carcinoma (CH27) cells by downregulating CDK4 and cyclin D1, as well as upregulating cyclin E
CDK4↓,
cycD1/CCND1↓,
cycE/CCNE↑,
BAX↑, SGC-7901 cells showed that when baicalein was administered, Bcl-2 was downregulated and Bax was increased
Bcl-2↓,
VEGF↓, Baicalein inhibits the synthesis of vascular endothelial growth factor (VEGF), HIF-1, c-Myc, and nuclear factor kappa B (NF-κB) in the G1 and S phases of ovarian cancer cell
Hif1a↓,
cMyc↓,
NF-kB↓,
ROS↑, Baicalein produced intracellular reactive oxygen species (ROS) and activated BNIP3 to slow down the development and hasten the apoptosis of MG-63,OS cell
BNIP3↑,
*neuroP↑, Baicalein exhibits neuroprotective qualities against amyloid (AN) functions by preventing AN from aggregating in PC12 neuronal cells to cause A𝛽-induced cytotoxicity
*cognitive↑, baicalein encourages non-amyloidogenic processing of APP, which lowers the generation of A𝛽 and enhances cognitive function
*NO↓, baicalein effectively reduced NO generation and iNOS gene expression
*iNOS↓,
*COX2↓, Baicalein therapy significantly decreased the expression of COX-2 and iNOS, as well as PGE2 and NF-κB, indicating a protective effect against cerebral I/R injury.
*PGE2↓,
*NRF2↑, Baicalein therapy markedly elevated nuclear Nrf2 expression and AMPK phosphorylation in the ischemic cerebral cortex
*p‑AMPK↑,
*Ferroptosis↓, Baicalein suppressed ferroptosis associated with 12/15-LOX, hence lessening the severity of post-traumatic epileptic episodes generated by FeCl3
*lipid-P↓, HT22 cells were damaged by ferroptosis, which is mitigated by baicalein may be due to its lipid peroxidation inhibitor
*ALAT↓, Baicalin lowers the raised levels of hepatic markers alanine transaminase (ALT), aspartate aminotransferase (AST)
*AST↓,
*Fas↓, Baicalin has also been shown to suppress apoptosis, decrease FAS protein expression, block the caspase-8 pathway, and decrease Bax protein production
*BAX↓,
*Apoptosis↓,

2289- Ba,  Rad,    Baicalein Inhibits the Progression and Promotes Radiosensitivity of Esophageal Squamous Cell Carcinoma by Targeting HIF-1A
- in-vitro, ESCC, KYSE150
TumCP↓, Radiation combined with baicalein could significantly inhibit the proliferation and migration of esophageal cancer cells compared with that of 6 Gy rays alone
TumCMig↓,
Glycolysis↓, 20μM baicalein reduced glycolysis in KYSE150 cells
cycD1/CCND1↓,
CDK4↓,
ECAR↓, Baicalein reduces ECAR and glycoPER
TumCCA↑, baicalein arrested cells in the G1 phase of the cell cycle
HK1↓, HK1 (4QS9),13 ALDH2, GPI and ALDOA are the key enzymes in the process of glycolysis.
ALDH↓,
ALDOA↓,
PKM2↓, protein levels of HIF-1A and PKM2 decreased significantly after baicalein treatment.
Hif1a↓,

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

5551- BBM,    Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF-κB Axis
- vitro+vivo, Bladder, NA
tumCV↓, our results showed that berbamine inhibited cell viability, colony formation, and proliferation.
TumCP↓,
TumCCA↑, Additionally, berbamine induced cell cycle arrest at S phase by a synergistic mechanism involving stimulation of P21 and P27 protein expression
P21↑,
p27↑,
cycD1/CCND1↓, as well as downregulation of CyclinD, CyclinA2, and CDK2 protein expression.
cycA1/CCNA1↓,
CDK2↓,
EMT↓, In addition to suppressing epithelial-mesenchymal transition (EMT), berbamine rearranged the cytoskeleton to inhibit cell metastasis.
TumMeta↓,
p65↓, Mechanistically, the expression of P65, P-P65, and P-IκBα was decreased upon berbamine treatment
p‑p65↓,
IKKα↓,
NF-kB↑, berbamine attenuated the malignant biological activities of BCa cells by inhibiting the NF-κB pathway.
ROS↑, More importantly, berbamine increased the intracellular reactive oxygen species (ROS) level through the downregulation of antioxidative genes such as Nrf2, HO-1, SOD2, and GPX-1.
NRF2↓,
HO-1↓,
SOD2↓,
GPx1↓,
Bax:Bcl2↑, increase in the ratio of Bax/Bcl-2.
TumVol↓, berbamine successfully inhibited tumor growth and blocked the NF-κB pathway in our xenograft model

5553- BBM,    A review on berbamine–a potential anticancer drug
- Review, Var, NA
P-gp↓, Treatment with berbamine decreased P-glycoprotein (P-gp) expression and down-regulated expression of MDR1 (multi-drug resistance1) and survivin mRNA in K562/A02 cells
MDR1↓,
survivin↓,
NF-kB↓, decrease expression of nuclear factor-B (NF-B), phosphoIB, IKK, and survivin.
TumCP↓, In a chronic myeloid leukemia cell line KU812, berbamine inhibited cell proliferation in a time- and dose-dependent manner, with IC50 values for treatments of 24, 48, and 72 h at 5.83, 3.43, and 0.75 μg/ml, respectively.
TumCCA↑, Berbamine induced cell cycle arrest at the G1 phase and also induced apoptosis.
Apoptosis↑,
SMAD3↑, The compound up-regulated transcriptions of Smad3 and p21, and increased protein levels of both total Smad3 and phosphorylated Smad3.
P21↑,
cycD1/CCND1↓, The protein levels of cyclin D1 and c-Myc were reduced.
cMyc↑,
Bcl-2↓, The levels of the anti-apoptotic proteins Bcl-2 and Bcl-xL were decreased, and the level of the pro-apoptotic protein Bax was increased.
Bcl-xL↓,
BAX↑,
CaMKII ↓, The compound has been shown to specifically bind to the ATP-binding pocket of calmodulin kinase (CAMK)II, inhibit its phosphorylation, and trigger apoptosis.
ChemoSen↑, Berbamine also significantly enhanced the activity of anticancer drugs like trichostatin A and celecoxib.
MMP2↓, EBB down-regulated the activities and mRNA levels of matrix metalloproteinases (MMP) 2 and 9, and up-regulated the mRNA levels of tissue inhibitor of metalloproteinases (TIMP) 1.
MMP9↓,
TIMP1↑,
cl‑Casp3↑, induction of apoptosis, including activation and cleavage of caspases 3, 8, 9 and PARP.
cl‑Casp9↑,
cl‑Casp8↑,
cl‑PARP↑,
IL6↓, BBD inhibited autocrine IL-6 production, and down-regulated membrane IL-6 receptor (IL-6R) expression.
ROS↑, Production of reactive oxygen species (ROS) was increased by BBMD3 in these cells.

1379- BBR,    Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells
- in-vitro, lymphoma, NA
TumCP↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
TumCCA↑, G0/G1 phase
MMP↓,
Ca+2↑,
ATP↓, decreased intracellular adenosine triphosphate production,
mtDam↑, mitochondrial dysfunction
Apoptosis↑,
ROS↑,
JNK↑,
eff↓, treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358.

2335- BBR,    Chemoproteomics reveals berberine directly binds to PKM2 to inhibit the progression of colorectal cancer
- in-vitro, CRC, HT29 - in-vitro, CRC, HCT116 - in-vivo, NA, NA
PKM2↓, berberine is directly bound to pyruvate kinase isozyme type M2 (PKM2) in colorectal cancer cells. Berberine inhibited PKM2 activity
Glycolysis↓, berberine was shown to inhibit the reprogramming of glucose metabolism and the phosphorylation of STAT3, down regulate the expression of Bcl-2 and Cyclin D1 genes
p‑STAT3↓,
Bcl-2↓,
cycD1/CCND1↓,
TumCG↓, n vivo experiments showed that tumor growth was inhibited in HT29 cell-bearing mice injected intraperitoneally with berberine (5 or 10 mg/kg body weight)
Ki-67↓, Berberine inhibited the proliferation index (Ki67 expression)
lactateProd↓, Berberine inhibited lactate production, glucose uptake, pyruvate production, and PKM2 activity in HWT tumor tissues, but no apparent effects were observed in both F244A mutant cells and I199S mutant tumor tissues
glucose↓,

2678- BBR,    Berberine as a Potential Agent for the Treatment of Colorectal Cancer
- Review, CRC, NA
*Inflam↓, BBR exerts remarkable anti-inflammatory (94–96), antiviral (97), antioxidant (98), antidiabetic (99), immunosuppressive (100), cardiovascular (101, 102), and neuroprotective (103) activities.
*antiOx↑,
*cardioP↑,
*neuroP↑,
TumCCA↑, BBR could induce G1 cycle arrest in A549 lung cancer cells by decreasing the levels of cyclin D1 and cyclin E1
cycD1/CCND1↓,
cycE/CCNE↓,
CDC2↓, BBR also induced G1 cycle arrest by inhibiting cyclin B1 expression and CDC2 kinase in some cancer cells
AMPK↝, BBR has been suggested to induce autophagy in glioblastoma by targeting the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)/ULK1 pathway
mTOR↝,
Casp8↑, BBR has been revealed to stimulate apoptosis in leukemia by upregulation of caspase-8 and caspase-9
Casp9↑,
Cyt‑c↑, in skin squamous cell carcinoma A431 cells by increasing cytochrome C levels
TumCMig↓, BBR has been confirmed to inhibit cell migration and invasion by inhibiting the expression of epithelial–mesenchymal transition (EMT)
TumCI↓,
EMT↓,
MMPs↓, metastasis-related proteins, such as matrix metalloproteinases (MMPs) and E-cadherin,
E-cadherin↓,
Telomerase↓, BBR has shown antitumor effects by interacting with microRNAs (125) and inhibiting telomerase activity
*toxicity↓, Numerous studies have revealed that BBR is a safe and effective treatment for CRC
GRP78/BiP↓, Downregulates GRP78
EGFR↓, Downregulates EGFR
CDK4↓, downregulates CDK4, TERT, and TERC
COX2↓, Reduces levels of COX-2/PGE2, phosphorylation of JAK2 and STAT3, and expression of MMP-2/-9.
PGE2↓,
p‑JAK2↓,
p‑STAT3↓,
MMP2↓,
MMP9↓,
GutMicro↑, BBR can inhibit tumor growth through meditation of the intestinal flora and mucosal barrier, and generally and ultimately improve weight loss. BBR has been reported to modulate the composition of intestinal flora and significantly reduce flora divers
eff↝, BBR can regulate the activity of P-glycoprotein (P-gp), and potential drug-drug interactions (DDIs) are observed when BBR is coadministered with P-gp substrates
*BioAv↓, the efficiency of BBR is limited by its low bioavailability due to its poor absorption rate in the gut, low solubility in water, and fast metabolism. Studies have shown that the oral bioavailability of BBR is 0.68% in rats
BioAv↑, combining it with p-gp inhibitors (such as tariquidar and tetrandrine) (196, 198), and modification to berberine organic acid salts (BOAs)

2686- BBR,    Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs
- Review, Nor, NA
Inflam↓, BBR has documented to have anti-diabetic, anti-inflammatory and anti-microbial (both anti-bacterial and anti-fungal) properties.
IL6↓, BBRs can inhibit IL-6, TNF-alpha, monocyte chemo-attractant protein 1 (MCP1) and COX-2 production and expression.
MCP1↓,
COX2↓,
PGE2↓, BBRs can also effect prostaglandin E2 (PGE2)
MMP2↓, and decrease the expression of key genes involved in metastasis including: MMP2 and MMP9.
MMP9↓,
DNAdam↑, BBR induces double strand DNA breaks and has similar effects as ionizing radiation
eff↝, In some cell types, this response has been reported to be TP53-dependent
Telomerase↓, This positively-charged nitrogen may result in the strong complex formations between BBR and nucleic acids and induce telomerase inhibition and topoisomerase poisoning
Bcl-2↓, BBR have been shown to suppress BCL-2 and expression of other genes by interacting with the TATA-binding protein and the TATA-box in certain gene promoter regions
AMPK↑, BBR has been shown in some studies to localize to the mitochondria and inhibit the electron transport chain and activate AMPK.
ROS↑, targeting the activity of mTOR/S6 and the generation of ROS
MMP↓, BBR has been shown to decrease mitochondrial membrane potential and intracellular ATP levels.
ATP↓,
p‑mTORC1↓, BBR induces AMPK activation and inhibits mTORC1 phosphorylation by suppressing phosphorylation of S6K at Thr 389 and S6 at Ser 240/244
p‑S6K↓,
ERK↓, BBR also suppresses ERK activation in MIA-PaCa-2 cells in response to fetal bovine serum, insulin or neurotensin stimulation
PI3K↓, Activation of AMPK is associated with inhibition of the PI3K/PTEN/Akt/mTORC1 and Raf/MEK/ERK pathways which are associated with cellular proliferation.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt. In HCT116 cells, PTEN inhibits Akt signaling and proliferation.
Akt↓,
Raf↓,
MEK↓,
Dose↓, The effects of low doses of BBR (300 nM) on MIA-PaCa-2 cells were determined to be dependent on AMPK as knockdown of the alpha1 and alpha2 catalytic subunits of AMPK prevented the inhibitory effects of BBR on mTORC1 and ERK activities and DNA synthes
Dose↑, In contrast, higher doses of BBR inhibited mTORC1 and ERK activities and DNA synthesis by AMPK-independent mechanisms [223,224].
selectivity↑, BBR has been shown to have minimal effects on “normal cells” but has anti-proliferative effects on cancer cells (e.g., breast, liver, CRC cells) [225–227].
TumCCA↑, BBR induces G1 phase arrest in pancreatic cancer cells, while other drugs such as gemcitabine induce S-phase arrest
eff↑, BBR was determined to enhance the effects of epirubicin (EPI) on T24 bladder cancer cells
EGFR↓, In some glioblastoma cells, BBR has been shown to inhibit EGFR signaling by suppression of the Raf/MEK/ERK pathway but not AKT signaling
Glycolysis↓, accompanied by impaired glycolytic capacity.
Dose?, The IC50 for BBR was determined to be 134 micrograms/ml.
p27↑, Increased p27Kip1 and decreased CDK2, CDK4, Cyclin D and Cyclin E were observed.
CDK2↓,
CDK4↓,
cycD1/CCND1↓,
cycE/CCNE↓,
Bax:Bcl2↑, Increased BAX/BCL2 ratio was observed.
Casp3↑, The mitochondrial membrane potential was disrupted and activated caspase 3 and caspases 9 were observed
Casp9↑,
VEGFR2↓, BBR treatment decreased VEGFR, Akt and ERK1,2 activation and the expression of MMP2 and MMP9 [235].
ChemoSen↑, BBR has been shown to increase the anti-tumor effects of tamoxifen (TAM) in both drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells.
eff↑, The combination of BBR and CUR has been shown to be effective in suppressing the growth of certain breast cancer cell lines.
eff↑, BBR has been shown to synergize with the HSP-90 inhibitor NVP-AUY922 in inducing death of human CRC.
PGE2↓, BBR inhibits COX2 and PEG2 in CRC.
JAK2↓, BBR prevented the invasion and metastasis of CRC cells via inhibiting the COX2/PGE2 and JAK2/STAT3 signaling pathways.
STAT3↓,
CXCR4↓, BBR has been observed to inhibit the expression of the chemokine receptors (CXCR4 and CCR7) at the mRNA level in esophageal cancer cells.
CCR7↓,
uPA↓, BBR has also been shown to induce plasminogen activator inhibitor-1 (PAI-1) and suppress uPA in HCC cells which suppressed their invasiveness and motility.
CSCs↓, BBR has been shown to inhibit stemness, EMT and induce neuronal differentiation in neuroblastoma cells. BBR inhibited the expression of many genes associated with neuronal differentiation
EMT↓,
Diff↓,
CD133↓, BBR also suppressed the expression of many genes associated with cancer stemness such as beta-catenin, CD133, NESTIN, N-MYC, NOTCH and SOX2
Nestin↓,
n-MYC↓,
NOTCH↓,
SOX2↓,
Hif1a↓, BBR inhibited HIF-1alpha and VEGF expression in prostate cancer cells and increased their radio-sensitivity in in vitro as well as in animal studies [290].
VEGF↓,
RadioS↑,

4658- BBR,    Berberine Suppresses Stemness and Tumorigenicity of Colorectal Cancer Stem-Like Cells by Inhibiting m6A Methylation
- in-vitro, CRC, HCT116 - in-vitro, CRC, HT29
CSCs↓, Our observation that Berberine effectively decreased m6A methylation by decreasing β-catenin and subsequently increased FTO suggests a role of Berberine in modulating stemness and malignant behaviors in colorectal CSCs.
TumCP↓, Berberine treatment decreased cell proliferation by decreasing cyclin D1 and increasing p27 and p21 and subsequently induced cell cycle arrest at the G1/G0 phase.
cycD1/CCND1↓,
p27↑,
P21↑,
TumCCA↑,
Apoptosis↑, Berberine treatment also decreased colony formation and induced apoptosis.
ChemoSen↑, Berberine treatment also increased chemosensitivity in CSCs and promoted chemotherapy agent-induced apoptosis.
β-catenin/ZEB1↓, Berberine treatment increased FTO by decreasing β-catenin, which is a negative regulator of FTO.
FTO↑,
CD44↓, Consistently, CD44 and CD133 were decreased by Berberine treatment
CD133↓,
ChemoSen↑, Berberine Enhanced Chemosensitivity via Regulating FTO

5178- BBR,    Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
TumCP↑, Here, we report that in vitro treatment of androgen-insensitive (DU145 and PC-3) and androgen-sensitive (LNCaP) prostate cancer cells with berberine inhibited cell proliferation and induced cell death in a dose-dependent (10–100 μmol/L) and time-depe
TumCCA↑, associated with G1-phase arrest, which in DU145 cells was associated with inhibition of expression of cyclins D1, D2, and E and cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 proteins,
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
P21↑, increased expression of the Cdk inhibitory proteins (Cip1/p21 and Kip1/p27), and enhanced binding of Cdk inhibitors to Cdk.
p27↑,
Apoptosis↑, Berberine also significantly (P < 0.05–0.001) enhanced apoptosis of DU145 and LNCaP cells with induction of a higher ratio of Bax/Bcl-2 proteins
Bax:Bcl2↑,
MMP↓, disruption of mitochondrial membrane potential, and activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase.
Casp9↑,
Casp3↑,
PARP↑,
DNAdam↑, analysis of DNA fragmentation
selectivity↑, Berberine Inhibits Proliferation and Viability and Induces the Death of Prostate Cancer Cells but not of Normal Prostate Epithelial Cells
Cyt‑c↑, Berberine Induces the Disruption of Mitochondrial Membrane Potential and Increases the Release of Cytochrome c

5176- BBR,    Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice
- vitro+vivo, CRC, HCT116 - in-vitro, CRC, SW480 - in-vitro, CRC, LoVo
TumVol↓, berberine treated mice showed a 60% reduction in tumor number
Ki-67↓, Berberine also decreased AOM/DSS induced Ki-67 and COX-2 expression
COX2↓,
AMPK↑, Berberine activated AMP-activated protein kinase (AMPK), a major regulator of metabolic pathways, and inhibited mammalian target of rapamycin (mTOR),
mTOR↓, Berberine Inhibits mTOR Signaling in CRC Cells
NF-kB↓, Berberine inhibited Nuclear Factor kappa-B (NF-κB) activity, reduced the expression of cyclin D1 and survivin, induced phosphorylation of p53 and increased caspase-3 cleavage in vitro.
cycD1/CCND1↓,
survivin↓,
P53↑,
cl‑Casp3↑,
TumCP↓, berberine suppresses colon epithelial proliferation and tumorigenesis via AMPK dependent inhibition of mTOR activity and AMPK independent inhibition of NF-κB.
Inflam↓, Berberine Inhibits AOM/DSS-induced Inflammation and Proliferation
COX2↓, We found COX-2 expression to be significantly decreased in berberine treated animals on day 70
ACC↑, Berberine Activates AMPK and Acetyl-CoA Carboxylase (ACC) in CRC Cells

2745- BetA,    Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors
- in-vitro, CRC, RKO - in-vitro, CRC, SW480 - in-vivo, NA, NA
Apoptosis↑, BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft
TumCG↓,
Sp1/3/4↓, BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells
survivin↓, decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1.
VEGF↓,
p65↓,
EGFR↓,
cycD1/CCND1↓,
ROS↑, due to induction of reactive oxygen species (ROS),
MMP↓, BA decreases MMP and induces ROS in RKO cells.

1285- BetA,    Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits proliferation, migration and induces apoptosis in cancer cells
- in-vitro, Var, NA
Apoptosis↑,
Bcl-2↓,
cycD1/CCND1↓,
BAX↑,

5721- BF,    Bufalin Suppresses Triple-Negative Breast Cancer Stem Cell Growth by Inhibiting the Wnt/β-Catenin Signaling Pathway
- in-vitro, BC, NA
CSCs↓, Bufalin effectively suppressed TNBCSC self-renewal in in vitro tumorsphere assays and significantly reduced tumor growth in an in vivo HCC1937 TNBCSC xenograft chorioallantoic membrane (CAM) model.
TumCCA↑, Bufalin induced G0/G1 phase cell cycle arrest by downregulating key regulatory proteins, including c-myc, cyclin D1, and CDK4.
cMyc↓,
cycD1/CCND1↓,
CDK4↓,
MMP↓, It also promoted intrinsic apoptosis through nuclear fragmentation, mitochondrial membrane potential reduction, and caspase activation.
Casp↑,
CD133↓, bufalin downregulated key CSC markers, such as CD133, CD44, ALDH1A1, Nanog, Oct4, and Sox2.
CD44↓,
ALDH1A1↓,
Nanog↓,
OCT4↓,
SOX2↓,
Wnt↓, Notably, bufalin suppressed the Wnt/β-catenin signaling pathway by reducing β-catenin mRNA and protein expression, leading to the downregulation of EGFR, a downstream target of Wnt signaling.
β-catenin/ZEB1↓,
EGFR↓,

5653- BNL,    Borneol hinders the proliferation and induces apoptosis through the suppression of reactive oxygen species-mediated JAK1 and STAT-3 signaling in human prostate cancer cells
- in-vitro, Pca, PC3
ROS↑, BNL treatment with PC-3 cells induces cytotoxicity, increases ROS production, and causes apoptotic morphological changes in a concentration-dependent manner.
TumCP↓, BNL significantly reduced the expression of cell proliferation markers such as cyclin-D1, cyclin-D2 and cyclin-E1 (P<0.05) compared to untreated PC-3 control cells.
cycD1/CCND1↓,
cycE1↓,
Apoptosis↑, BNL treatment enhanced apoptosis rates by observed overexpression of Bcl-2-associated X protein (Bax), caspase-3
BAX↓,
Casp3↑,
Bcl-2↓, and down regulation B-cell leukemia/lymphoma 2 (Bcl-2) (P<0.05) expression in PC-3 cells.
IL6↓, Additionally, BNL reduced interleukin-6, JAK1, and STAT3 phosphorylation ((P<0.05) in PC-3 cells
JAK1↓,
STAT3↓, Thus, BNL may be a therapeutic agent against prostate cancer by blocking the STAT3 signaling axis.

2776- Bos,    Anti-inflammatory and anti-cancer activities of frankincense: Targets, treatments and toxicities
- Review, Var, NA
*5LO↓, Arthritis Human primary chondrocytes: 5-LOX↓, TNF-α↓, MMP3↓
*TNF-α↓,
*MMP3↓,
*COX1↓, COX-1↓, Leukotriene synthesis by 5-LOX↓
*COX2↓, Arthritis Human blood in vitro: COX-2↓, PGE2↓, TH1 cytokines↓, TH2 cytokines↑
*PGE2↓,
*Th2↑,
*Catalase↑, Ethanol-induced gastric ulcer: CAT↑, SOD↑, NO↑, PGE-2↑
*SOD↑,
*NO↑,
*PGE2↑,
*IL1β↓, inflammation Human PBMC, murine RAW264.7 macrophages: TNFα↓ IL-1β↓, IL-6↓, Th1 cytokines (IFNγ, IL-12)↓, Th2 cytokines (IL-4, IL-10)↑; iNOS↓, NO↓, phosphorylation of JNK and p38↓
*IL6↓,
*Th1 response↓,
*Th2↑,
*iNOS↓,
*NO↓,
*p‑JNK↓,
*p38↓,
GutMicro↑, colon carcinogenesis: gut microbiota; pAKT↓, GSK3β↓, cyclin D1↓
p‑Akt↓,
GSK‐3β↓,
cycD1/CCND1↓,
Akt↓, Prostate Ca: AKT and STAT3↓, stemness markers↓, androgen receptor↓, Sp1 promoter binding↓, p21(WAF1/CIP1)↑, cyclin D1↓, cyclin D2↓, DR5↑,CHOP↑, caspases-3/-8↑, PARP cleavage, NFκB↓, IKK↓, Bcl-2↓, Bcl-xL↓, caspase 3↑, DNA
STAT3↓,
CSCs↓,
AR↓,
P21↑,
DR5↑,
CHOP↑,
Casp3↑,
Casp8↑,
cl‑PARP↑,
DNAdam↑,
p‑RB1↓, Glioblastoma: pRB↓, FOXM1↓, PLK1↓, Aurora B/TOP2A pathway↓,CDC25C↓, pCDK1↓, cyclinB1↓, Aurora B↓, TOP2A↓, pERK-1/-2↓
FOXM1↓,
TOP2↓,
CDC25↓,
p‑CDK1↓,
p‑ERK↓,
MMP9↓, Pancreas Ca: Ki-67↓, CD31↓, COX-2↓, MMP-9↓, CXCR4↓, VEGF↓
VEGF↓,
angioG↓, Apoptosis↑, G2/M arrest, angiogenesis↓
ROS↑, ROS↑,
Cyt‑c↑, Leukemia : cytochrome c↑, AIF↑, SMAC/DIABLO↑, survivin↓, ICAD↓
AIF↑,
Diablo↑,
survivin↓,
ICAD↓,
ChemoSen↑, Breast Ca: enhancement in combination with doxorubicin
SOX9↓, SOX9↓
ER Stress↑, Cervix Ca : ER-stress protein GRP78↑, CHOP↑, calpain↑
GRP78/BiP↑,
cal2↓,
AMPK↓, Breast Ca: AMPK/mTOR signaling↓
mTOR↓,
ROS↓, Boswellia extracts and its phytochemicals reduced oxidative stress (in terms of inhibition of ROS and RNS generation)

2775- Bos,    The journey of boswellic acids from synthesis to pharmacological activities
- Review, Var, NA - Review, AD, NA - Review, PSA, NA
ROS↑, modulation of reactive oxygen species (ROS) formation and the resulting endoplasmic reticulum stress is central to BA’s molecular and cellular anticancer activities
ER Stress↑,
TumCG↓, Cell cycle arrest, growth inhibition, apoptosis induction, and control of inflammation are all the effects of BA’s altered gene expression
Apoptosis↑,
Inflam↓,
ChemoSen↑, BA has additional synergistic effects, increasing both the sensitivity and cytotoxicity of doxorubicin and cisplatin
Casp↑, BA decreases viability and induces apoptosis by activat- ing the caspase-dependent pathway in human pancreatic cancer (PC) cell lines
ERK↓, BA might inhibit the activation of Ak strain transforming (Akt) and extracellular signal–regulated kinase (ERK)1/2,
cl‑PARP↑, initiation of cleavage of PARP were prompted by the treatment with AKBA
AR↓, AKBA affects the androgen receptor by reducing its expression,
cycD1/CCND1↓, decrease in cyclin D1, which inhibits cellular proliferation
VEGFR2↓, In prostate cancer, the downregulation of vascular endothelial growth factor receptor 2–mediated angiogenesis caused by BA
CXCR4↓, Figure 6
radioP↑,
NF-kB↓,
VEGF↓,
P21↑,
Wnt↓,
β-catenin/ZEB1↓,
Cyt‑c↑,
MMP2↓,
MMP1↓,
MMP9↓,
PI3K↓,
MAPK↓,
JNK↑,
*5LO↓, Table 1 (non cancer)
*NRF2↑,
*HO-1↑,
*MDA↓,
*SOD↑,
*hepatoP↑, Preclinical studies demonstrated hepatoprotective impact for BA against different models of hepatotoxicity via tackling oxidative stress, and inflammatory and apoptotic indices
*ALAT↓,
*AST↓,
*LDH↑,
*CRP↓,
*COX2↓,
*GSH↑,
*ROS↓,
*Imm↑, oral administration of biopolymeric fraction (BOS 200) from B. serrata in mice led to immunostimulatory effects
*Dose↝, BA at low concentration tend to stimulate an immune response, as those utilized in the study of Beghelli et al. (2017) however, utilizing higher concentration suppressed the immune response
*eff↑, Useful actions on skin and psoriasis
*neuroP↑, AKBA has substantially diminished the levels of inflammatory markers such as 5-LOX, TNF-, IL-6, and meliorated cognition in lipopolysaccharide-induced neuroinflammation rodent models
*cognitive↑,
*IL6↓,
*TNF-α↓,

2767- Bos,    The potential role of boswellic acids in cancer prevention and treatment
- Review, Var, NA
*Inflam↓, profound application as a traditional remedy for various ailments, especially inflammatory diseases including asthma, arthritis, cerebral edema, chronic pain syndrome, chronic bowel diseases, cancer
AntiCan↑,
*MAPK↑, 11-keto-BAs can stimulate Mitogen-activated protein kinases (MAPK) and mobilize the intracellular Ca(2+) that are important for the activation of human polymorphonuclear leucocytes (PMNL)
*Ca+2↝,
p‑ERK↓, AKBA prohibited the phosphorylation of extracellular signal-regulated kinase-1 and -2 (Erk-1/2) and impaired the motility of meningioma cells stimulated with platelet-derived growth factor BB
TumCI↓,
cycD1/CCND1↓, In the case of colon cancer, BA treatment on HCT-116 cells led to a decrease in cyclin D, cyclin E, and Cyclin-dependent kinases such as CDK2 and CDK4, along with significant reduction in phosphorylated Rb (pRb)
cycE/CCNE↓,
CDK2↓,
CDK4↓,
p‑RB1↓,
*NF-kB↓, convey inhibition of NF-kappaB and subsequent down-regulation of TNF-alpha expression in activated human monocytes
*TNF-α↓,
NF-kB↓, PC-3 prostate cancer cells in vitro and in vivo by inhibiting constitutively activated NF-kappaB signaling by intercepting the activity of IkappaB kinase (IKK
IKKα↓,
MCP1↓, LPS-challenged ApoE-/- mice via inhibition of NF-κB and down regulation of MCP-1, MCP-3, IL-1alpha, MIP-2, VEGF, and TF
IL1α↓,
MIP2↓,
VEGF↓,
Tf↓,
COX2↓, pancreatic cancer cell lines, AKBA inhibited the constitutive expression of NF-kB and caused suppression of NF-kB regulated genes such as COX-2, MMP-9, CXCR4, and VEGF
MMP9↓,
CXCR4↓,
VEGF↓,
eff↑, AKBA and aspirin revealed that AKBA has higher potential via modulation of the Wnt/β-catenin pathway, and NF-kB/COX-2 pathway in adenomatous polyps
PPARα↓, AKBA is also responsible for down-regulation of PPAR-alpha and C/EBP-alpha in a dose and temporal dependent manner in mature adipocytes, ultimately leading to pparlipolysis
lipid-P?,
STAT3↓, activation of STAT-3 in human MM cells could be inhibited by AKBA
TOP1↓, (PKBA; a semisynthetic analogue of 11-keto-β-boswellic acid), had been reported to influence the activity of topoisomerase I & II,
TOP2↑,
5HT↓, (5-LO), responsible for catalyzing the synthesis of leukotrienes from arachidonic acid and human leucocyte elastase (HLE), and serine proteases involved in several inflammatory processes, is considered to be a potent molecular target of BA derivative
p‑PDGFR-BB↓, BA up-regulates SHP-1 with subsequent dephosphorylation of PDGFR-β and downregulation of PDGF-dependent signaling after PDGF stimulation, thereby exerting an anti-proliferative effect on HSCs hepatic stellate cells
PDGF↓,
AR↓, AKBA targets different receptors that include androgen receptor (AR), death receptor 5 (DR5), and vascular endothelial growth factor receptor 2 (VEGFR2), and leads to the inhibition of proliferation of prostate cancer cells
DR5↑, induced expression of DR4 and DR5.
angioG↓, via apoptosis induction and suppression of angiogenesis
DR4↑,
Casp3↑, AKBA resulted in activation of caspase-3 and caspase-8, and initiation of poly (ADP) ribose polymerase (PARP) cleavage.
Casp8↑,
cl‑PARP↑,
eff↑, AKBA was preincubated with LY294002 or wortmannin (inhibitors of PI3K), it caused a significant enhancement of apoptosis in HT-29 cells
chemoPv↑, chemopreventive response of AKBA was estimated against intestinal adenomatous polyposis through the inhibition of the Wnt/β-catenin and NF-κB/cyclooxygenase-2 signaling pathway
Wnt↓,
β-catenin/ZEB1↓,
ascitic↓, AKBA by the suppression of ascites,
Let-7↑, AKBA could up-regulate the expression of let-7 and miR-200
miR-200b↑,
eff↑, anti-tumorigenic effects of curcumin and AKBA on the regulation of specific cancer-related miRNAs in colorectal cancer cells, and confirmed their protective action
MMP1↓, . It can inhibit the expression of MMP-1, MMP-2, and MMP-9 mRNAs along with secretions of TNF-α and IL-1β in THP-1 cells.
MMP2↓,
eff↑, combined administration of metformin, an anti-diabetic drug, and boswellic acid nanoparticles exhibited significant synergism through the inhibition of MiaPaCa-2 pancreatic cancer cell proliferation
BioAv↓, BA as a therapeutic drug is its poor bioavailability
BioAv↑, administration of BSE-018 concomitantly with a high-fat meal led to several-fold increased areas under the plasma concentration-time curves as well as peak concentrations of beta-boswellic acid (betaBA)
Half-Life↓, drug needs to be given orally at the interval of six hours due to its calculated half- life, which was around 6 hrs.
toxicity↓, BSE has been found to be a safe drug without any adverse side reactions, and is well tolerated on oral administration.
Dose↑, Boswellia serrata extract to the maximum amount of 4200 mg/day is not toxic and it is safe to use though it shows poor bioavailability
BioAv↑, Approaches like lecithin delivery form (Phytosome®), nanoparticle delivery systems like liposomes, emulsions, solid lipid nanoparticles, nanostructured lipid carriers, micelles and poly (lactic-co-glycolic acid) nanoparticles
ChemoSen↑, Like any other natural products BA can also be effective as chemosensitizer

2773- Bos,    Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: Potential role in prevention and therapy of cancer
- Review, Var, NA
Inflam↓, BA has been shown to be effective against chronic inflammation-driven diseases such as adjuvant or bovine serum albumin-induced arthritis, osteoarthritis, Crohn’s disease, ulcerative colitis, and ileitis, and galactosamine/endotoxin-induced hepa
TumCCA↑, BA induced apoptosis was mediated by cell cycle arrest in the G1 phase and by activating caspases 3, 8 and 9 in HT-29 cells
Casp3↑,
Casp8↑,
Casp9↑,
STAT3↑, BA inhibited the growth of multiple myeloma cells by suppression of STAT3 pathway and by activation of protein tyrosine phosphatase SHP1
SHP1↓,
NF-kB↓, BA down regulated the expression of NF-kB, cyclin D1, COX2, Ki-67, CD-31 and IAPs in the tumor tissue.
cycD1/CCND1↓,
COX2↓,
Ki-67↓,
CD31↓,
IAP1↓,
MMPs↓, AKBA induced cell cycle arrest was mediated by down-regulating the expression of cyclinD1, suppresses MMP activity, and also induced apoptosis by suppressing Bcl-2, and Bcl-xL expression
Bcl-2↓,
Bcl-xL↓,

1169- Bos,    Boswellic Acid Inhibits Growth and Metastasis of Human Colorectal Cancer in Orthotopic Mouse Model By Downregulating Inflammatory, Proliferative, Invasive, and Angiogenic Biomarkers
- in-vivo, CRC, NA
TumCG↓,
TumVol↓,
Weight∅, without significant decreases in body weight
ascitic↓,
TumMeta↓,
Ki-67↓,
CD31↓,
NF-kB↓,
COX2↓,
Bcl-2↓,
Bcl-xL↓,
IAP1↓,
survivin↓,
cycD1/CCND1↓,
ICAM-1↓,
MMP9↓,
CXCR4↓,
VEGF↓,

1427- Bos,    Acetyl-keto-β-boswellic acid inhibits cellular proliferation through a p21-dependent pathway in colon cancer cells
- in-vitro, CRC, HT-29 - in-vitro, CRC, HCT116 - in-vitro, CRC, LS174T
TumCG↓,
TumCCA↑, G1 phase
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
p‑RB1↓,
P21↑,

1422- Bos,    Boswellic acid exerts antitumor effects in colorectal cancer cells by modulating expression of the let-7 and miR-200 microRNA family
- in-vitro, CRC, NA - in-vivo, NA, NA
5LO↓, boswellic acids, is known to be a non-redox and non-competitive inhibitor of 5-lipoxygenase
TumCG↓,
Let-7↑,
miR-200b↑, AKBA significantly up-regulated expression of the let-7 and miR-200 families in various CRC cell lines
NF-kB↓,
cMyc↓,
cycD1/CCND1↓,
MMP9↓,
CXCR4↓,
VEGF↓,
Bcl-xL↓,
survivin↓,
IAP1↓,
XIAP↓,
TumCG↓,
CDK6↓,
Vim↓,
E-cadherin↑,

1426- Bos,  CUR,  Chemo,    Novel evidence for curcumin and boswellic acid induced chemoprevention through regulation of miR-34a and miR-27a in colorectal cancer
- in-vivo, CRC, NA - in-vitro, CRC, HCT116 - in-vitro, CRC, RKO - in-vitro, CRC, SW480 - in-vitro, RCC, SW-620 - in-vitro, RCC, HT-29 - in-vitro, CRC, Caco-2
miR-34a↑, curcumin and AKBA induced upregulation of tumor-suppressive miR-34a and downregulation of miR-27a in CRC cells
miR-27a-3p↓,
TumCG↓,
BAX↑,
Bcl-2↓,
PARP1↓,
TumCCA↑,
Apoptosis↑,
cMyc↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
ChemoSen↑, combined treatment further increased the inhibitory effects
miR-34a↑, miR-34a expression was upregulated by curcumin and further elevated by concurrent treatment with curcumin and AKBA in HCT116 cell
miR-27a-3p↓,


Showing Research Papers: 1 to 50 of 251
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 251

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 3,   GPx1↓, 1,   GPx4↓, 2,   GSH↓, 3,   HK1↓, 1,   HO-1↓, 1,   c-Iron↑, 1,   lipid-P?, 1,   lipid-P↑, 1,   MDA↑, 1,   NRF2↓, 2,   ROS↓, 1,   ROS↑, 22,   ROS⇅, 1,   SOD↓, 1,   SOD2↓, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 1,   Tf↓, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↑, 1,   AIF↑, 2,   ATP↓, 2,   CDC2↓, 1,   CDC25↓, 3,   MEK↓, 1,   MMP↓, 9,   mtDam↑, 1,   Raf↓, 2,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

12LOX↓, 2,   ACC↑, 1,   ACSL4↑, 1,   ALDOA↓, 1,   AMPK↓, 1,   AMPK↑, 3,   AMPK↝, 1,   cMyc↓, 8,   cMyc↑, 1,   ECAR↓, 1,   glucose↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 3,   H2S↑, 1,   lactateProd↓, 2,   LDH↓, 1,   NADPH↓, 1,   NADPH↑, 1,   PKM2↓, 4,   PPARα↓, 1,   p‑S6K↓, 1,  

Cell Death ⓘ

Akt↓, 9,   p‑Akt↓, 2,   Apoptosis↑, 18,   mt-Apoptosis↑, 1,   BAX↓, 1,   BAX↑, 16,   Bax:Bcl2↑, 4,   Bcl-2↓, 17,   Bcl-xL↓, 8,   Casp↑, 4,   Casp12↑, 1,   Casp3↓, 1,   Casp3↑, 12,   cl‑Casp3↑, 4,   Casp7↑, 1,   Casp8↑, 7,   cl‑Casp8↑, 1,   Casp9↑, 8,   cl‑Casp9↑, 1,   Chk2↑, 1,   p‑Chk2↑, 1,   CK2↓, 1,   Cyt‑c↑, 11,   Diablo↑, 1,   DR4↑, 1,   DR5↑, 3,   Fas↑, 2,   Ferroptosis↑, 3,   hTERT/TERT↓, 1,   IAP1↓, 3,   ICAD↓, 1,   JNK↓, 1,   JNK↑, 3,   MAPK↓, 2,   MAPK↑, 1,   Mcl-1↓, 1,   MDM2↓, 1,   oncosis↑, 1,   p27↑, 9,   p38↑, 2,   survivin↓, 9,   Telomerase↓, 3,  

Kinase & Signal Transduction ⓘ

CaMKII ↓, 1,   HER2/EBBR2↓, 2,   SOX9↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

miR-27a-3p↓, 2,   tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↓, 1,   ER Stress↑, 5,   GRP78/BiP↓, 1,   GRP78/BiP↑, 2,  

Autophagy & Lysosomes ⓘ

BNIP3↑, 1,   LC3II↑, 1,   p62↓, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

p‑ATM↑, 1,   p‑ATR↑, 1,   CHK1↓, 1,   p‑CHK1↑, 1,   DNAdam↑, 10,   HR↓, 1,   p16↑, 2,   P53↑, 4,   p‑P53↑, 1,   PARP↑, 2,   p‑PARP↑, 1,   cl‑PARP↑, 8,   PARP1↓, 1,   PCNA↓, 2,   RAD51↓, 1,   p‑γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   p‑CDK1↓, 1,   CDK1/2/5/9∅, 1,   CDK2↓, 10,   CDK4↓, 18,   cycA1/CCNA1↓, 1,   cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 2,   CycB/CCNB1↑, 1,   cycD1/CCND1↓, 50,   CycD3↓, 1,   cycE/CCNE↓, 11,   cycE/CCNE↑, 2,   cycE1↓, 2,   E2Fs↓, 1,   P21↑, 15,   p‑RB1↓, 3,   TumCCA↑, 31,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   ALDH1A1↓, 1,   CD133↓, 3,   CD44↓, 2,   cMET↓, 1,   CSCs↓, 6,   Diff↓, 1,   EMT↓, 7,   ERK↓, 4,   p‑ERK↓, 4,   FOXM1↓, 1,   FOXO3↑, 1,   Gli↓, 1,   GSK‐3β↓, 3,   HDAC↓, 1,   HDAC1↓, 1,   HDAC10↓, 1,   HDAC3↓, 1,   IGF-1↓, 1,   Let-7↑, 2,   miR-34a↑, 2,   mTOR↓, 4,   mTOR↝, 1,   p‑mTOR↓, 1,   p‑mTORC1↓, 1,   n-MYC↓, 1,   Nanog↓, 1,   Nestin↓, 1,   NOTCH↓, 1,   NOTCH1↓, 1,   OCT4↓, 1,   PI3K↓, 8,   PTEN↑, 2,   Shh↓, 1,   SHP1↓, 1,   SOX2↓, 2,   STAT3↓, 9,   STAT3↑, 1,   p‑STAT3↓, 2,   TOP1↓, 1,   TOP2↓, 2,   TOP2↑, 1,   TumCG↓, 11,   Wnt↓, 5,   Wnt/(β-catenin)↓, 1,  

Migration ⓘ

5LO↓, 1,   AP-1↓, 1,   Ca+2↑, 5,   cal2↓, 1,   CD31↓, 2,   Cdc42↑, 1,   CDK4/6↓, 2,   E-cadherin↓, 1,   E-cadherin↑, 4,   FAK↓, 1,   FTO↑, 1,   ITGB1↑, 1,   Ki-67↓, 4,   miR-200b↑, 2,   miR-29b↑, 1,   MMP1↓, 2,   MMP2↓, 12,   MMP7↓, 1,   MMP9↓, 14,   MMPs↓, 2,   NCAM↑, 1,   PDGF↓, 1,   PKCδ↓, 1,   ROCK1↓, 1,   SMAD3↑, 1,   TGF-β↓, 3,   TIMP1↑, 1,   TIMP2↑, 2,   TumCI↓, 3,   TumCMig↓, 3,   TumCP↓, 15,   TumCP↑, 1,   TumMeta↓, 3,   Twist↓, 1,   uPA↓, 4,   Vim↓, 2,   β-catenin/ZEB1↓, 7,  

Angiogenesis & Vasculature ⓘ

angioG↓, 7,   EGFR↓, 5,   HIF-1↓, 1,   Hif1a↓, 7,   KDR/FLK-1↓, 1,   NO↓, 1,   p‑PDGFR-BB↓, 1,   VEGF↓, 17,   VEGFR2↓, 2,  

Barriers & Transport ⓘ

GLUT1↓, 1,   P-gp↓, 3,  

Immune & Inflammatory Signaling ⓘ

CCR7↓, 1,   COX2↓, 12,   COX2↑, 1,   CXCR4↓, 6,   ICAM-1↓, 1,   IKKα↓, 3,   p‑IKKα↓, 1,   IL1↓, 1,   IL12↑, 1,   IL1α↓, 1,   IL1β↓, 1,   IL1β↑, 1,   IL2↓, 1,   IL2↑, 1,   IL6↓, 6,   IL8↓, 3,   Imm↑, 1,   Inflam↓, 5,   JAK1↓, 1,   JAK2↓, 2,   p‑JAK2↓, 1,   MCP1↓, 2,   MIP2↓, 2,   NF-kB↓, 19,   NF-kB↑, 2,   p50↓, 1,   p65↓, 2,   p‑p65↓, 1,   PD-L1↓, 2,   PGE2↓, 4,   PSA↓, 1,   TNF-α↓, 1,   TNF-α↑, 2,  

Synaptic & Neurotransmission ⓘ

5HT↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 4,   CDK6↓, 6,   CDK6↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 4,   BioAv↑, 6,   BioAv↝, 1,   BioEnh↑, 3,   ChemoSen↑, 18,   Dose?, 1,   Dose↓, 1,   Dose↑, 2,   Dose∅, 1,   eff↓, 4,   eff↑, 12,   eff↝, 4,   Half-Life↓, 3,   MDR1↓, 2,   P450↓, 1,   RadioS↑, 2,   selectivity↑, 5,  

Clinical Biomarkers ⓘ

AR↓, 4,   ascitic↓, 2,   EGFR↓, 5,   Ferritin↓, 1,   FOXM1↓, 1,   GutMicro↑, 2,   HER2/EBBR2↓, 2,   hTERT/TERT↓, 1,   IL6↓, 6,   Ki-67↓, 4,   LDH↓, 1,   PD-L1↓, 2,   PSA↓, 1,  

Functional Outcomes ⓘ

AntiCan↓, 1,   AntiCan↑, 6,   chemoP↑, 1,   chemoPv↑, 2,   QoL↑, 1,   radioP↑, 1,   toxicity↓, 1,   toxicity↑, 1,   TumVol↓, 4,   Weight∅, 1,  
Total Targets: 310

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 1,   Ferroptosis↓, 1,   GSH↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 3,   ROS↓, 2,   SOD↑, 2,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 2,   p‑AMPK↑, 1,   LDH↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↓, 1,   BAX↓, 1,   Fas↓, 1,   Ferroptosis↓, 1,   iNOS↓, 3,   p‑JNK↓, 1,   MAPK↑, 1,   p38↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,  

Migration ⓘ

5LO↓, 2,   Ca+2↝, 1,   MMP3↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,   NO↓, 2,   NO↑, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   COX2↓, 4,   CRP↓, 1,   IL1β↓, 1,   IL6↓, 2,   Imm↑, 1,   Inflam↓, 3,   NF-kB↓, 1,   PGE2↓, 2,   PGE2↑, 1,   Th1 response↓, 1,   Th2↑, 2,   TNF-α↓, 3,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   Dose↝, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 2,   AST↓, 2,   CRP↓, 1,   GutMicro↑, 1,   IL6↓, 2,   LDH↑, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   chemoP↑, 1,   cognitive↑, 2,   hepatoP↑, 2,   neuroP↑, 4,   RenoP↑, 1,   toxicity↓, 1,  
Total Targets: 60

Scientific Paper Hit Count for: cycD1/CCND1, cyclin D1 pathway
20 Quercetin
19 Thymoquinone
13 Curcumin
11 Lycopene
9 Boswellia (frankincense)
9 Fisetin
9 Resveratrol
7 Berberine
6 Chrysin
6 Garcinol
6 Honokiol
5 Silver-NanoParticles
5 Artemisinin
5 Baicalein
5 Ellagic acid
5 Magnolol
5 salinomycin
5 Silymarin (Milk Thistle) silibinin
5 Shikonin
4 Apigenin (mainly Parsley)
4 Caffeic acid
4 Piperlongumine
3 Cisplatin
3 Metformin
3 Capsaicin
3 Carvacrol
3 EGCG (Epigallocatechin Gallate)
3 HydroxyTyrosol
3 Luteolin
3 Propolis -bee glue
3 Sulforaphane (mainly Broccoli)
3 Vitamin K2
2 Sorafenib (brand name Nexavar)
2 Astragalus
2 Allicin (mainly Garlic)
2 Astaxanthin
2 Berbamine
2 Betulinic acid
2 Chemotherapy
2 Carnosic acid
2 Celastrol
2 Ferulic acid
2 Gallic acid
2 Graviola
2 Niclosamide (Niclocide)
2 Phenethyl isothiocyanate
2 VitK3,menadione
2 Rosmarinic acid
2 Ursolic acid
1 2-DeoxyGlucose
1 Alpha-Lipoic-Acid
1 Andrographis
1 Gemcitabine (Gemzar)
1 Ashwagandha(Withaferin A)
1 Radiotherapy/Radiation
1 Bufalin/Huachansu
1 borneol
1 Butyrate
1 Caffeine
1 Caffeic Acid Phenethyl Ester (CAPE)
1 Chlorogenic acid
1 Chlorophyllin
1 Docosahexaenoic Acid
1 diet Methionine-Restricted Diet
1 Disulfiram
1 Copper and Cu NanoParticles
1 Evodiamine
1 Emodin
1 Gambogic Acid
1 Germacranolide
1 Siegesbeckia glabrescens
1 Baicalin
1 Inositol
1 Ivermectin
1 lambertianic acid
1 Licorice
1 Melatonin
1 Mushroom Chaga
1 Mushroom Shiitake, AHCC
1 Myricetin
1 Naringin
1 Orlistat
1 Plumbagin
1 Pterostilbene
1 doxorubicin
1 Paclitaxel
1 Selenite (Sodium)
1 Urolithin
1 Vitamin C (Ascorbic Acid)
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#:73  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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