BAD Cancer Research Results

BAD, BCL2 associated agonist of cell death: Click to Expand ⟱
Source:
Type:
BCL2 associated agonist of cell death (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family.
Expression of the BAD is associated with the development and progression of cancer.
Scientific Papers found: Click to Expand⟱
1360- Ash,  immuno,    Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer
- in-vitro, Lung, H1650 - in-vitro, Lung, A549 - in-vitro, CRC, HCT116 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
PD-L1↑,
eff↓, The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process.
ROS↑,
ER Stress↑,
Apoptosis↑,
BAX↑,
Bak↑,
BAD↑,
Bcl-2↓,
XIAP↓,
survivin↓,
cl‑PARP↑,
CHOP↑,
p‑eIF2α↑, phosphorylation of the eukaryotic initiation factor eIF-2
ICD↑,
eff↑, WFA Sensitizes LLC Syngeneic Mouse Tumors to α-PD-L1 In Vivo

1398- BBR,    Berberine inhibits the progression of renal cell carcinoma cells by regulating reactive oxygen species generation and inducing DNA damage
- in-vitro, Kidney, NA
TumCP↓,
TumCMig↓,
ROS↑,
Apoptosis↑,
BAX↑,
BAD↑,
Bak↑,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp9↑,
E-cadherin↑,
TIMP1↑,
γH2AX↑,
Bcl-2↓,
N-cadherin↓,
Vim↓,
Snail↓,
RAD51↓,
PCNA↓,

2691- BBR,    Berberine induces FasL-related apoptosis through p38 activation in KB human oral cancer cells
- in-vitro, Oral, KB
tumCV↓, viability of KB cells was found to decrease significantly in the presence of berberine in a dose-dependent manner.
DNAdam↑, berberine induced the fragmentation of genomic DNA, changes in cell morphology, and nuclear condensation.
Casp3↑, caspase-3 and -7 activation, and an increase in apoptosis were observed.
Casp7↑,
FasL↑, Berberine was also found to upregulate significantly the expression of the death receptor ligand, FasL
Casp8↑, triggered the activation of pro-apoptotic factors such as caspase-8, -9 and -3 and poly(ADP-ribose) polymerase (PARP).
Casp9↑,
PARP↑,
BAX↑, Bax, Bad and Apaf-1 were also significantly upregulated by berberine.
BAD↑,
APAF1↑,
MMP2↓, We also found that berberine-induced migration suppression was mediated by downregulation of MMP-2 and MMP-9 through phosphorylation of p38 MAPK.
MMP9↓,
p‑p38↑, This suggests that berberine-induced activation of the p38 and ERK1/2 MAPK pathways is the principal pathway involved in the apoptosis mediated by berberine in KB cells.
ERK↑,
MAPK↑,

2753- BetA,    Betulinic acid induces apoptosis by regulating PI3K/Akt signaling and mitochondrial pathways in human cervical cancer cells
- in-vitro, Cerv, HeLa
PI3K↓, BA treatment acted through downregulating a phosphatidylinositol 3-kinase (PI3K) subunit and suppressing the Akt phosphorylation at Thr308 and Ser473 after increasing the generation of intracellular reactive oxygen species
p‑Akt↓,
ROS↑,
TumCCA↑, BA induced cell cycle arrest at the G0/G1 phase, which was consistent with the cell cycle-related protein results in which BA significantly enhanced the expression of p27Kip and p21Waf1/Cip1 in HeLa cells.
p27↑,
P21↑,
mt-Apoptosis↑, mitochondrial apoptosis, as reflected by the increased expression of Bad and caspase-9
BAD↑,
Casp9↑,
MMP↓, decline in mitochondrial membrane potential.
eff↓, preincubation of the cells with glutathione (antioxidant) blocked the process of apoptosis, prevented the phosphorylation of downstream substrates.

5893- CAR,  TV,    Thymol and Carvacrol: Molecular Mechanisms, Therapeutic Potential, and Synergy With Conventional Therapies in Cancer Management
- Review, Var, NA
*Inflam↓, Monoterpenes like thymol and carvacrol are recognized for their anti‐inflammatory and anticancer properties,
AntiCan↑,
PI3K↓, Thymol derivatives, such as 1,2,3‐triazoles and carvacrol, effectively target breast cancer (BC) through PI3K/AKT/mTOR and NOTCH pathways and inhibit PIK3CA expression.
Akt↓,
mTOR↓,
NOTCH↓,
PIK3CA↓,
EGFR↓, thymol exhibits anti‐EGFR activity, while carvacrol modulates the HIF‐1α/VEGF pathway, making them potential candidates for colorectal cancer (CRC) management.
Hif1a↓,
VEGF↓,
ChemoSen↑, Their synergistic potential with chemotherapy, radiotherapy, and other bioactive compounds strengthens their therapeutic promise.
RadioS↑,
eff↝, challenges such as stability, bioavailability, and the need for clinical trials hinder their clinical application.
*cardioP↑, cardioprotective (Joshi et al. 2023), neuroprotective (Forqani et al. 2023) and hepato‐nephroprotective
*neuroP↑,
*hepatoP↑,
Apoptosis↑, Induction of Apoptosis
MMP↓, The apoptosis was due to ROS production, variations in the mitochondrial membrane, caspase‐3 activation, and DNA damage
Casp3↑,
ROS↑,
DNAdam↑,
eff↑, Thymol derivative, known as compound 10 (IC50 6.17 μM) exhibited 3.2‐fold more inhibition than 5‐fluorouracil (IC50 20.09 μM) against MCF‐7
BAX↑, Carvacrol (25, 50, 75, and 90 μM) enhanced the expression of Bax, Bad, Fas‐L, and cytochrome c, activated caspase‐9/3 and caspase‐8, induced cell cycle at G0/G1
BAD↑,
FasL↑,
Cyt‑c↑,
Casp9↑,
Casp8↑,
TumCCA↑,
P21↑, improved the expression of proteins (p21, cyclin D1, CDK4), and downregulated the SMO and GLI1 proteins expression in CC
Smo↓,
Gli1↓,
JNK↑, Moreover, thymol activated JNK and p38 MAPK while impeding the ERK pathway
ERK↓,
MAPK↓, Besides thymol, carvacrol has also been reported to inhibit MAPK or ERK pathways in previous studies.
TRPM7↓, inhibited TRPM7 expression in liver fibrotic C57BL/6J mice
Wnt/(β-catenin)↓, hymol inhibited HCT116 and LoVo cell line invasion via downregulating the Wnt/β‐catenin pathway and reducing c‐Myc and Cyclin D1 expression
BioAv↝, thymol and carvacrol are volatile, and their stability is influenced by these factors (temperature, light, oxygen, and pH)
BioAv↑, Ultrasonication is an effective technique to enhance the stability of thymol and other bioactive compounds. 400 watts of power elevated the performance of NC‐CH formulations, and NC‐CH‐400 displayed increased solubility.

448- CUR,    Heat shock protein 27 influences the anti-cancer effect of curcumin in colon cancer cells through ROS production and autophagy activation
- in-vitro, CRC, HT-29
Apoptosis↑,
TumCCA↑, G2/M cell cycle arrest
p‑Akt↓,
Akt↓,
Bcl-2↓,
p‑BAD↓,
BAD↑,
cl‑PARP↑,
ROS↑,
HSP27↑,
Beclin-1↑,
p62↑,
GPx1↓,
GPx4↓,

989- EGCG,  Citrate,    In vitro and in vivo study of epigallocatechin-3-gallate-induced apoptosis in aerobic glycolytic hepatocellular carcinoma cells involving inhibition of phosphofructokinase activity
- in-vitro, HCC, NA - in-vivo, NA, NA
PFK↓,
Glycolysis↓, only inhibited glycolysis in cancer cells with a high rate of aerobic glycolysis (HCC-LM3 and HepG2 cells) but not in low-glycolytic cells (Huh-7 and LO2 cells).
lactateProd↓,
GlucoseCon↓,
TumCP↓,
TumCCA↑, arrests cells in S Phage
Casp3↑, citrate enhanced the EGCG upregulation of active caspase-3 and cleaved-PARP in both HCC-LM3 and HepG2 cells
cl‑PARP↑,
Apoptosis↑,
Casp8↑,
Casp9↑,
Cyt‑c↝, translocation of cytochrome c from the mitochondria into the cytosol
MMP↓,
BAD↑,
GLUT2↓, figure2 c,d
PKM2∅, figure2 c,d

3205- EGCG,    The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseas
- Review, Var, NA - Review, AD, NA
Beclin-1↑, EGCG not only regulates autophagy via increasing Beclin-1 expression and reactive oxygen species generation,
ROS↑,
Apoptosis↑, Apoptosis is a common cell function in biology and is induced by endoplasmic reticulum stress (ERS)
ER Stress↑,
*Inflam↓, EGCG has health benefits including anti-tumor [15], anti-inflammatory [16], anti-diabetes [17], anti-myocardial infarction [18], anti-cardiac hypertrophy [19], anti-atherosclerosis [20], and antioxidant
*cardioP↑,
*antiOx↑,
*LDL↓, These effects are mainly related to (LDL) cholesterol inhibition, NF-κB inhibition, MPO activity inhibition, decreased levels of glucose and glycated hemoglobin in plasma, decreased inflammatory markers, and reduced ROS generation
*NF-kB↓,
*MPO↓,
*glucose↓,
*ROS↓,
ATG5↑, EGCG induced autophagy by enhancing Beclin-1, ATG5, and LC3B and promoted mitochondrial depolarization in breast cancer cells.
LC3B↑,
MMP↑,
lactateProd↓, 20 mg kg−1 EGCG significantly decreased glucose, lactic acid, and vascular endothelial growth factor (VEGF) levels
VEGF↓,
Zeb1↑, (20 uM) inhibited the proliferation through activating autophagy via upregulating ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibiting TP53, MYC, and CASP8 genes in SSC-4 human oral squamous cells [
Wnt↑,
IGF-1R↑,
Fas↑,
Bak↑,
BAD↑,
TP53↓,
Myc↓,
Casp8↓,
LC3II↑, increasing the LC3-II expression levels and induced apoptosis via inducing ROS in mesothelioma cell lines,
NOTCH3↓, but also could reduce partially Notch3/DLL3 to reduce drug-resistance and the stemness of tumor cells
eff↑, In combination therapies, low-intensity pulsed electric field (PEF) can improve EGCG to affect tumor cells; ultrasound (US) with tumor cells is the application of physical stimulation in cancer therapy.
p‑Akt↓, 20 μM EGCG increased intracellular ROS levels and LC3-II, and inhibited p-Akt in PANC-1 cells
PARP↑, 100 μM EGCG increased LC3-II, activated caspase-3 and PARP, and reduced p-Akt in HepG2
*Cyt‑c↓, EGCG protected neuronal cells against human viruses by inhibiting cytochrome c and Bax translocations, and reducing autophagy with increased LC3-II expression and decreased p62 expression
*BAX↓,
*memory↑, EGCG restored autophagy in the mTOR/p70S6K pathway to weaken memory and learning disorders induced by CUMS
*neuroP↑, Finally, EGCG increased the neurological scores through inhibiting cell death
*Ca+2?, EGCG treatment, [Ca2+]m and [Ca2+]i expressions were reduced and oxyhemoglobin-induced mitochondrial dysfunction lessened.
GRP78/BiP↑, MMe cells with EGCG treatment improved GRP78 expression in the endoplasmic reticulum, and induced EDEM, CHOP, XBP1, and ATF4 expressions, and increased the activity of caspase-3 and caspase-8.
CHOP↑, GRP78 accumulation converted UPR of MMe cells into pro-apoptotic ERS
ATF4↑,
Casp3↑,
Casp8↑,
UPR↑,

2849- FIS,    Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells
- in-vitro, Melanoma, U266
TumCD↑, Fisetin elicited the cytotoxicity in U266 cells, manifested as an increased fraction of the cells with sub-G1 content or stained positively with TUNEL labeling
TumCCA↑,
Casp3↑, Fisetin enhanced caspase-3 activation, downregulation of Bcl-2 and Mcl-1L, and upregulation of Bax, Bim and Bad
Bcl-2↓,
Mcl-1↓,
BAX↑,
BIM↑,
BAD↑,
AMPK↑, Fisetin activated AMPK as well as its substrate acetyl-CoA carboxylase (ACC), along with a decreased phosphorylation of AKT and mTOR.
ACC↑,
p‑Akt↓,
p‑mTOR↓,
ROS↑, Fisetin also stimulated generation of ROS in U266 cells
eff↓, Conversely, compound C or N-acetyl-l-cystein blocked fisetin-induced apoptosis

2857- FIS,    A review on the chemotherapeutic potential of fisetin: In vitro evidences
- Review, Var, NA
COX2↓, fisetin altered the expression of cyclooxygenase 2 (COX2) thereby suppressed the secretion of prostaglandin E2 ultimately resulting in the inhibition of epidermal growth factor receptor (EGFR) and NF-κB in human colon cancer cells HT29
PGE2↓,
EGFR↓,
Wnt↓, fisetin treatment inhibited the stimulation of Wnt signaling pathway via downregulating the expression of β-catenin and Tcell factor (TCF) 4
β-catenin/ZEB1↓,
TCF↑,
Apoptosis↑, fisetin triggers apoptosis in U266 cells through multiple pathways: enhancing the activation of caspase-3 and PARP cleavage, decreasing the expression of anti-apoptotic proteins (Bcl-2 and Mcl-1 L ),
Casp3↑,
cl‑PARP↑,
Bcl-2↓,
Mcl-1↓,
BAX↑, ncreasing the expression of pro-apoptotic proteins (Bax, Bim, and Bad)
BIM↑,
BAD↑,
Akt↓, decreasing the phosphorylation of AKT and mTOR and elevating the expression of acetyl CoA carboxylase (ACC
mTOR↓,
ACC↑,
Cyt‑c↑, release the cytochrome c and Smac/Diablo into the cytosol
Diablo↑,
cl‑Casp8↑, fisetin exhibited an increased level of cleaved caspase-8, Fas/Fas ligand, death receptor 5/TRAIL, and p53 levels in HCT-116 cells
Fas↑,
DR5↑,
TRAIL↑,
Securin↓, Securin gets degraded on exposure to fisetin in colon cancer cells.
CDC2↓, fisetin decreased the expression of cell division cycle proteins (CDC2 and CDC25C)
CDC25↓,
HSP70/HSPA5↓, Fisetin induced apoptosis as a result of the downregulation of HSP70 and BAG3 and the inhibition of Bcl-2, Bcl-x L and Mcl-1. T
CDK2↓, AGS 0, 25, 50, 75 μM – 24 and 48 h ↓CDK2, ↓CDK4, ↓cyclin D1, ↑casapse-3 cleavage
CDK4↓,
cycD1/CCND1↓,
MMP2↓, A549 0, 1, 5, 10 μM- 24 and 48 hr: ↓MMP-2, ↓u-PA, ↓NF- κB, ↓c-Fos, ↓c-Jun
uPA↓,
NF-kB↓,
cFos↓,
cJun↓,
MEK↓, ↓ MEK1/2 and ERK1/2 phosphorylation, ↓N-cadherin, ↓vimentin, ↓snail, ↓fibronectin, ↑E-cadherin, ↑desmoglein
p‑ERK↓,
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↓,
NF-kB↑, increased expression of NF-κB p65 leading to apoptosis was due to ROS generation on exposure to fisetin
ROS↑,
DNAdam↑, increased ROS triggered cell death through PARP cleavage, DNA damage and mitochondrial membrane depolarization.
MMP↓,
CHOP↑, Though fisetin upregulated CHOP expression and increased the production of ROS, these events fail to induce apoptosis in Caki cells.
eff↑, 50 μM fisetin + 1 mM melatonin Sk-mel-28 Enhances anti-tumour activity [54] 20 μM fisetin + 1 mM melatonin MeWo Enhances anti-tumour activity [54] 10 μM fisetin + 0.1 μM melatonin A549 Induces autophagic cell death
ChemoSen↑, 20 μM fisetin + 5 μM sorafenib A375, SK-MEL-28 Suppresses invasion and metastasis [44] 40 μM fisetin + 10 μM cisplatin A549, A549-CR Enhances apoptosis

2844- FIS,    Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells
- in-vitro, OS, U2OS
tumCV↓, Fisetin at 20-100 µM effectively reduced the viability of OS cells, and induced apoptosis by signifi-cantly inducing the expression of Caspases- 3,-8 and -9 and pro-apoptotic proteins (Bax and Bad) with subsequent down-regulation of Bcl-xL and Bcl-2
Apoptosis↑,
Casp3↑,
Casp8↑,
Casp9↑,
BAX↑,
BAD↑,
Bcl-2↓,
Bcl-xL↓,
PI3K↓, inhibited PI3K/Akt pathway and ERK1/2,
Akt↓,
ERK↓,
p‑JNK↑, it caused enhanced expressions of p-JNK, p-c-Jun and p-p38
p‑cJun↑,
p‑p38↑,
ROS↑, Fisetin-induced ROS generation and decrease in mitochondrial membrane potential
MMP↓, noticeable decline of mitochondrial transmembrane potential (ΔΨm) in a dose-dependent manner
mTORC1↓, fisetin at various concentrations (20-100 μM) caused a significant (p<0.05) decrease in the level of p-Akt and mTORC1 (an important effector protein of Akt), while up-regulated PTEN.
PTEN↑,
p‑GSK‐3β↓, Level of phosphorylated glycogensynthase kinase 3ǃ (GSK3ǃ), (a serine/threonine kinase) and cyclin D1 were potentially decreased by fisetin which is in line with raised non-phosphorylated levels of GSK3ǃ
GSK‐3β↑,
NF-kB↓, Down-regualtion of NF-κB along with significant up-regulations in IκB upon fisetin treatment correlates with the down-regulation of p-Akt levels.
IKKα↑,
Cyt‑c↑, activates the efflux of cytochrome C

2845- FIS,    Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy
- Review, Var, NA
PI3K↓, block multiple signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and p38
Akt↓,
mTOR↓,
p38↓,
*antiOx↑, antioxidant, anti-inflammatory, antiangiogenic, hypolipidemic, neuroprotective, and antitumor effect
*neuroP↑,
Casp3↑, U266 cancer cell line through activation of caspase-3, downregulation of Bcl-2 and Mcl-1L, upregulation of Bax, Bim and Bad
Bcl-2↓,
Mcl-1↓,
BAX↑,
BIM↑,
BAD↑,
AMPK↑, activation of 5'adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and decreased phosphorylation of AKT and mTOR were also observed
ACC↑,
DNAdam↑, DNA fragmentation, mitochondrial membrane depolarizatio
MMP↓,
eff↑, fisetin in combination with a citrus flavanone, hesperetin mediated apoptosis by mitochondrial membrane depolarization and caspase-3 act
ROS↑, NCI-H460 human non-small cell lung cancer line, fisetin generated reactive oxygen species (ROS), endoplasmic reticulum (ER) stress
cl‑PARP↑, fisetin treatment resulted in PARP cleavage
Cyt‑c↑, release of cyt. c
Diablo↑, release of cyt. c and Smac/DIABLO from mitochondria,
P53↑, increased p53 protein levels
p65↓, reduced phospho-p65 and Myc oncogene expression
Myc↓,
HSP70/HSPA5↓, fisetin causes inhibition of proliferation by the modulation of heat shock protein 70 (HSP70), HSP27
HSP27↓,
COX2↓, anti-proliferative effects of fisetin through the activation of apoptosis via inhibition of cyclooxygenase-2 (COX-2) and Wnt/EGFR/NF-κB signaling pathways
Wnt↓,
EGFR↓,
NF-kB↓,
TumCCA↑, The anti-proliferative effects of fisetin and hesperetin were shown to be occurred through S, G2/M, and G0/G1 phase arrest in K562 cell progression
CDK2↓, decrease in levels of cyclin D1, cyclin A, Cdk-4 and Cdk-2
CDK4↓,
cycD1/CCND1↓,
cycA1/CCNA1↓,
P21↑, increase in p21 CIP1/WAF1 levels in HT-29 human colon cancer cell
MMP2↓, fisetin has exhibited tumor inhibitory effects by blocking matrix metalloproteinase-2 (MMP- 2) and MMP-9 at mRNA and protein levels,
MMP9↓,
TumMeta↓, Antimetastasis
MMP1↓, fisetin also inhibited the MMP-14, MMP-1, MMP-3, MMP-7, and MMP-9
MMP3↓,
MMP7↓,
MET↓, promotion of mesenchymal to epithelial transition associated with a decrease in mesenchymal markers i.e. N-cadherin, vimentin, snail and fibronectin and an increase in epithelial markers i.e. E-cadherin
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↑,
uPA↓, fisetin suppressed the expression and activity of urokinase plasminogen activator (uPA)
ChemoSen↑, combination treatment of fisetin and sorafenib reduced the migration and invasion of BRAF-mutated melanoma cells both in in-vitro
EMT↓, inhibited epithelial to mesenchymal transition (EMT) as observed by a decrease in N-cadherin, vimentin and fibronectin and an increase in E-cadherin
Twist↓, inhibited expression of Snail1, Twist1, Slug, ZEB1 and MMP-2 and MMP-9
Zeb1↓,
cFos↓, significant decrease in NF-κB, c-Fos, and c-Jun levels
cJun↓,
EGF↓, Fisetin inhibited epidermal growth factor (EGF)
angioG↓, Antiangiogenesis
VEGF↓, decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF, EGFR, COX-2
eNOS↓,
*NRF2↑, significantly increased nuclear translocation of Nrf2 and antioxidant response element (ARE) luciferase activity, leading to upregulation of HO-1 expression
HO-1↑,
NRF2↓, Fisetin also triggered the suppression of Nrf2
GSTs↓, declined placental type glutathione S-transferase (GST-p) level in the liver of the fisetin- treated rats with hepatocellular carcinoma (HCC)
ATF4↓, Fisetin also rapidly increased the levels of both Nrf2 and ATF4

1923- JG,    Mechanism of Juglone-Induced Cell Cycle Arrest and Apoptosis in Ishikawa Human Endometrial Cancer Cells
- in-vitro, Endo, NA
TumCP↓, juglone significantly inhibited Ishikawa cell proliferation
TumCCA↑, as shown by S phase arrest
cycA1/CCNA1↓, inactivation of cyclin A protein
ROS↑, The ROS levels increased significantly after exposure to juglone
P21↑, paralleled increases in the mRNA and protein expression of p21
CDK2↓, decreases in the levels of CDK2, cdc25A, CHK1, and cyclin A
CDK1↓,
CDC25↓,
Bcl-2↓, expression of Bcl-2 and Bcl-xL was significantly down-regulated,
Bcl-xL↓,
BAX↑, expression of Bax, Bad and cyto c was up-regulated
BAD↑,
Cyt‑c↑,

2912- LT,    Luteolin: a flavonoid with a multifaceted anticancer potential
- Review, Var, NA
ROS↑, induction of oxidative stress, cell cycle arrest, upregulation of apoptotic genes, and inhibition of cell proliferation and angiogenesis in cancer cells.
TumCCA↑,
TumCP↓,
angioG↓,
ER Stress↑, Luteolin induces mitochondrial dysfunction and activates the endoplasmic reticulum stress response in glioblastoma cells, which triggers the generation of intracellular reactive oxygen species (ROS)
mtDam↑,
PERK↑, activate the expression of stress-related proteins by mediating the phosphorylation of PERK, ATF4, eIF2α, and cleaved-caspase 12.
ATF4↑,
eIF2α↑,
cl‑Casp12↑,
EMT↓, Luteolin is known to reverse epithelial-to-mesenchymal transition (EMT), which is associated with the cancer cell progression and metastasis.
E-cadherin↑, upregulating the biomarker E-cadherin expression, followed by a significant downregulation of the N-cadherin and vimentin expression
N-cadherin↓,
Vim↓,
*neuroP↑, Furthermore, luteolin holds potential to improve the spinal damage and brain trauma caused by 1-methyl-4-phenylpyridinium due to its excellent neuroprotective properties.
NF-kB↓, downregulation and suppression of cellular pathways such as nuclear factor kappa B (NF-kB), phosphatidylinositol 3’-kinase (PI3K)/Akt, and X-linked inhibitor of apoptosis protein (XIAP)
PI3K↓,
Akt↑,
XIAP↓,
MMP↓, Furthermore, the membrane action potential of mitochondria depletes in the presence of luteolin, Ca2+ levels and Bax expression upregulate, the levels of caspase-3 and caspase-9 increase, while the downregulation of Bcl-2
Ca+2↑,
BAX↑,
Casp3↑,
Casp9↑,
Bcl-2↓,
Cyt‑c↑, cause the cytosolic release of cytochrome c from mitochondria
IronCh↑, Luteolin serves as a good metal-chelating agent owing to the presence of dihydroxyl substituents on the aromatic ring framework
SOD↓, luteolin further triggered an early phase accumulation of ROS due to the suppression of the activity of cellular superoxide dismutase.
*ROS↓, Luteolin reportedly demonstrated an optimal 43.7% inhibition of the accumulation of ROS, 24.5% decrease in malondialdehyde levels, and 38.7% lowering of lactate dehydrogenase levels at a concentration of 30 µM
*LDHA↑,
*SOD↑, expression of superoxide dismutase ameliorated by 73.7%, while the activity of glutathione improved by 72.3% at the same concentration of luteolin
*GSH↑,
*BioAv↓, Poor bioavailability of luteolin limits its optimal therapeutic efficacy and bioactivity
Telomerase↓, MDA-MB-231 cells with luteolin led to dose dependent arrest of cell cycle in S phase by reducing the levels of telomerase and by inhibiting the phosphorylation of NF-kB inhibitor α along with its target gene c-Myc
cMyc↓,
hTERT/TERT↓, These events led to the suppression of the expression of human telomerase reverse transcriptase (hTERT) encoding for the catalytic subunit of telomerase
DR5↑, luteolin upregulated the expression of caspase cascades and death receptors, including DR5
Fas↑, expression of proapoptotic genes such as FAS, FADD, BAX, BAD, BOK, BID, TRADD upregulates, while the anti-apoptotic genes NAIP, BCL-2, and MCL-1 experience downregulation.
FADD↑,
BAD↑,
BOK↑,
BID↑,
NAIP↓,
Mcl-1↓,
CDK2↓, expression of cell cycle regulatory genes CDK2, CDKN2B, CCNE2, CDKN1A, and CDK4 decreased on incubation with luteolin
CDK4↓,
MAPK↓, expression of MAPK1, MAPK3, MAP3K5, MAPK14, PIK3C2A, PIK3C2B, AKT1, AKT2, and ELK1 downregulated
AKT1↓,
Akt2↓,
*Beclin-1↓, luteolin led to downregulation of the expression of hypoxia-inducible factor-1α and autophagy-associated proteins, Beclin 1, and LC3
Hif1a↓,
LC3II↑, LC3-II is upregulated following the luteolin treatment in p53 wild type HepG2 cells i
Beclin-1↑, Luteolin treatment reportedly increased the number of intracellular autophagosomes, as indicated by an increased expression of Beclin 1, and conversion of LC3B-I to LC3B-II in hepatocellular carcinoma SMMC-7721 cells.

4519- MAG,    Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer
- Review, Var, NA
*antiOx↑, anti-oxidant [70], anti-inflammatory [71], anti-bacterial [10], anti-thrombotic or anti-platelet
*Inflam↓,
*Bacteria↓,
*AntiAg↑,
*BBB↑, MAG can easily cross the blood brain barrier
*BioAv↓, bioavailability is in the region of 10%
BAD↑, MAG increased the expression of Bad, Bcl-XS, caspases-3, -6, and -9 and c-Jun N-terminal kinases (JNK) and suppressed the expression of Bcl-xL
Casp3↑,
Casp6↑,
Casp9↑,
JNK↑,
Bcl-xL↓,
PTEN↑, MAG also induced apoptosis by enhancing the expression of PTEN and down-regulation of AKT
Akt↓,
NF-kB↓, MAG induces cell death and reduces cell proliferation by inhibition of NF-κB activity
MMP7↓, MAG inhibits cancer metastasis by reducing the expression of matrix metalloproteinase-7, -9 (MMP-7, -9) and urokinase plasminogen activator (uPA)
MMP9↓,
uPA↓,
Hif1a↓, MAG attenuated angiogenesis in vitro and in vivo which is mediated by inhibition of the expression of hypoxia-inducible factors-1α (HIF-1α) and vascular endothelial growth factor (VEGF) secretion in human bladder cancer cells
VEGF↓,
FOXO3↓, MAG downregulated the expression of transcriptional factor Forkhead box O3 (FoxO3), ubiquitin ligase, MuRF-1 and MAFbx/atrogin-1.
Ca+2↑, ↑Cytosolic free Ca (2+);
TumCCA↑, ↑Cell cycle arrest at G2/M phase, ROS, release of cyt-c,
ROS↑,
Cyt‑c↑,

4643- OLE,  HT,    Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine
- Review, Var, NA
TumCCA↑, A similar S phase cell cycle arrest was also observed for 800 μM HT, and induction of apoptosis also took place after 24 h incubation of HT-29 cells with 600 μM and 800 μM HT
Apoptosis↑,
ER Stress↑, 400 μM HT triggered endoplasmic reticulum stress in HT-29 cells, with activation of unfolded protein response,
UPR↑,
CHOP↑, increase in CHOP protein levels (responsible for ROS production and Bcl-2 downregulation) and NADPH oxidase 4 (NOX4)
ROS↑,
Bcl-2↓,
NOX4↑,
Hif1a↓, Moreover, 400 μM HT reduced HIF-1α protein levels
MMP2↓, figure 2
MMP↓,
VEGF↓,
Akt↓,
NF-kB↓,
p65↓,
SIRT3↓,
mTOR↓,
Catalase↓,
SOD2↓,
FASN↓,
STAT3↓,
HDAC2↓,
HDAC3↓,
BAD↑, figure 2 upregulated
BAX↑,
Bak↑,
Casp3↑,
Casp9↑,
PARP↑,
P53↑,
P21↑,
p27↑,
Half-Life↝, HT added to extra virgin olive oil produced a plasma peak of 3.79 ng/mL after 30 min, followed by a rapid decline in HT plasma concentration
BioAv↓, On the basis of these pieces of data, it becomes evident that cytotoxicity and anti-cancer effects of OLE and HT were recorded at concentrations largely exceeding those reachable with diet/olive oil consumption
BioAv↓, Thus, it is difficult to imagine how OLE and HT may be used as cancer-preventive/treating agents if the route of administration is ingestion.
selectivity↑, However, even at high concentrations, OLE and HT seem to be selectively cytotoxic for cancer cells, with no or negligible/minimal effects on non-cancer cells,
RadioS↑, 200 μM OLE enhanced cell radiosensitivity in vitro and in vivo after injection in BALB/C nude mice
*ROS↓, A lot of experimental data in vivo and in vitro have definitively demonstrated the ROS scavenger ability of OLE and HT, which can also act on antioxidant cellular mechanisms restoring ROS homeostasis,
*GSH↑, including promotion of the increase in reduced glutathione levels (GSH), depletion of lipid peroxidation product malondialdehyde (MDA), intensification of the expression and/or activity of detoxicating enzymes SOD, CAT, glutathione-S-transferase (GST
*MDA↓,
*SOD↑,
*Catalase↑,
*NRF2↑, and nuclear factor E2-related factor 2 (Nrf2) upregulation/transactivation,
*chemoP↑, OLE and HT have shown an important ability to mitigate the toxicity elicited by chemotherapeutic agents mainly through their largely demonstrated antioxidant and ROS scavenger activity.
*Inflam↓, OLE and HT exhibit an anti-inflammatory activity that has been demonstrated in multiple in vivo and in vitro models,
PPARγ↑, HT-dependent anti-inflammatory effect was also mediated by HT-elicited increase in protein levels of PPARγ

5218- PG,    Propyl gallate inhibits hepatocellular carcinoma cell growth through the induction of ROS and the activation of autophagy
- in-vitro, HCC, Hep3B
TumCP↓, PG inhibited HCC cell proliferation in vitro and in zebrafish models in vivo in a dose- and time-dependent manner.
Apoptosis↑, PG also induced cell apoptosis and increased the number of necrotic cells in a time- and dose-dependent manner as determined using a high-content analysis system.
ROS↑, PG also increased the intracellular levels of superoxide and reactive oxidative stress as well as the formation of autophagosomes and lysosomes.
TumAuto↑, but increased the rate of the LC3-I to LC3-II conversion, suggesting autophagy induction.
cl‑Casp3↑, PG exposure increased the levels of the pro-apoptotic proteins cleaved caspase-3, cleaved PARP, Bax, and Bad and a decreased level of the anti-apoptotic protein Bcl-2.
cl‑PARP↑,
BAX↑,
BAD↑,
Bcl-2↓,
toxicity↓, PG is a generally recognized as safe (GRAS) antioxidant in foods and cosmetic products at a maximum concentration of 0.1%. It is currently used as an antioxidant to protect food from peroxides induced rancidity
hepatoP↑, It could be of therapeutic value in protecting the liver from injury, inflammation, and carcinogenesis [46–51].
GSH↓, Interestingly, PG-induced GSH depletion and cell death in leukemia cells did not occur by increasing ROS levels in leukemia cells.

5208- PI,    Piperine Inhibits Cell Proliferation and Induces Apoptosis of Human Gastric Cancer Cells by Downregulating Phosphatidylinositol 3-Kinase (PI3K)/Akt Pathway
- in-vitro, GC, SNU16 - in-vitro, Nor, GES-1
TumCP↓, piperine inhibited proliferation and induced apoptosis of SNU-16 cells.
Apoptosis↑,
BAX↑, Piperine upregulated the protein expression of Bax, Bad, Cyto C, cleaved PARP, and cleaved caspase-3
BAD↑,
Cyt‑c↑,
cl‑PARP↑,
cl‑Casp3↑,
Bcl-2↓, but downregulated the protein expression of Bcl-2, Bcl-xl, pPI3k, and pAkt.
Bcl-xL↓,
p‑PI3K↓,
p‑Akt↓,
Ki-67↓, decreased Ki-67 expression in a dose-dependent manner.
toxicity↓, nontoxicity effect of piperine was confirmed by H&E staining analysis in kidney and heart tissues of mice.
RadioS↑, piperine pretreatment can suppress proliferation and activate apoptosis, thereby enhancing radiosensitization of colon cancer cells

86- QC,  PacT,    Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3)
- vitro+vivo, Pca, PC3
BAD↑, Quercetin up regulate mRNA and protein levels of Bad
IGFBP3↑,
Cyt‑c↑, Quercetin significantly increases the proapoptotic mRNA levels of Bad, IGFBP-3 and protein levels of Bad, cytochrome C, cleaved caspase-9, caspase-10, cleaved PARP and caspase-3 activity in PC-3 cells
cl‑Casp9↑, cleaved
Casp10↑,
cl‑PARP↑, Quercetin increases protein expression of cytochrome C and PARP
Casp3↑,
IGF-1R↓,
PI3K↓, PI3K expression significantly decreased after quercetin treatment
p‑Akt↓,
cycD1/CCND1↓, protein
IGF-1↓, mRNA levels of IGF-1,IGR-2, IGF-1R
IGF-2↓,
IGF-1R↓,
MMP↓, Apoptosis is confirmed by loss of mitochondrial membrane potential in quercetin treated PC-3 cells.
Apoptosis↑, uercetin treatment has been associated with antiproliferative effects [39] and induction of apop- tosis in cancer cells but not in normal cells [40].
NA?,

5327- TFdiG,    Theaflavin-3, 3'-digallate induces apoptosis and G2 cell cycle arrest through the Akt/MDM2/p53 pathway in cisplatin-resistant ovarian cancer A2780/CP70 cells
- in-vitro, Ovarian, A2780S
TumCG↓, exhibited a potent growth inhibitory effect on the cisplatin-resistant ovarian cancer A2780/CP70 cells (IC50, 23.81 μM),
selectivity↑, was less cytotoxic to a normal ovarian IOSE-364 cells (IC50, 59.58 μM)
TumCCA↑, TF3 induced preferential apoptosis and G2 cell cycle arrest in A2780/CP70 cells with respect to IOSE-364 cells.
Apoptosis↑,
P53↑, TF3 might upregulate the p53 expression via the Akt/MDM2 pathway.
BAX↑, TF3 significantly increased the protein levels of Bax, Bad and cleaved caspase-9
BAD↑,
cl‑Casp3↑,
p‑Akt↓, TF3 significantly decreased the phosphorylation of Akt without the influence on total Akt protein expression, and reduced the protein level of MDM2
MDM2↓,
MMP↓, Key events are the depolarization of the mitochondrial membrane potential and the release of mitochondrial factors such as cytochrome c into the cytosol
Cyt‑c↑,

2454- Trip,    Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ
- in-vitro, HNSCC, HaCaT - in-vivo, NA, NA
GSDME-N↑, Triptolide eliminates head and neck cancer cells through inducing gasdermin E (GSDME) mediated pyroptosis.
Pyro↑,
cMyc↓, TPL treatment suppresses expression of c-myc and mitochondrial hexokinase II (HK-II) in cancer cells
HK2↓,
BAD↑, leading to activation of the BAD/BAX-caspase 3 cascade and cleavage of GSDME by active caspase 3.
BAX↑,
Casp3↑,
NRF2↓, TPL treatment suppresses NRF2/SLC7A11 (also known as xCT) axis
xCT↓,
ROS↑, and induces reactive oxygen species (ROS) accumulation, regardless of the status of GSDME.
eff↑, Combination of TPL with erastin, an inhibitor of SLC7A11, exerts robust synergistic effect in suppression of tumor survival in vitro and in a nude mice model.
Glycolysis↓, TPL treatment repressed c-Myc/HK-II axis and aerobic glycolysis in head and neck cancer cells
GlucoseCon↓, as evidenced by reduced glucose consumption, lactate production and cellular ATP content following TPL treatment
lactateProd↓,
ATP↓,
xCT↓, TPL (50 nM) treatment decreased the protein levels of NRF2 and SLC7A11 (
eff↑, combination of TPL with erastin is a promising strategy for head and neck cancer therapy.


Showing Research Papers: 1 to 21 of 21

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 21

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned ⓘ

NA?, 1,  

Redox & Oxidative Stress ⓘ

Catalase↓, 1,   GPx1↓, 1,   GPx4↓, 1,   GSH↓, 1,   GSTs↓, 1,   HO-1↑, 1,   ICD↑, 1,   NOX4↑, 1,   NRF2↓, 2,   ROS↑, 16,   SIRT3↓, 1,   SOD↓, 1,   SOD2↓, 1,   xCT↓, 2,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   BOK↑, 1,   CDC2↓, 1,   CDC25↓, 2,   EGF↓, 1,   MEK↓, 1,   MMP↓, 10,   MMP↑, 1,   mtDam↑, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 3,   AKT1↓, 1,   AMPK↑, 2,   cMyc↓, 2,   FASN↓, 1,   GlucoseCon↓, 2,   GLUT2↓, 1,   Glycolysis↓, 2,   HK2↓, 1,   lactateProd↓, 3,   PFK↓, 1,   PIK3CA↓, 1,   PKM2∅, 1,   PPARγ↑, 1,  

Cell Death ⓘ

Akt↓, 7,   Akt↑, 1,   p‑Akt↓, 7,   APAF1↑, 1,   Apoptosis↑, 13,   mt-Apoptosis↑, 1,   BAD↑, 21,   p‑BAD↓, 1,   Bak↑, 4,   BAX↑, 15,   Bcl-2↓, 12,   Bcl-xL↓, 4,   BID↑, 1,   BIM↑, 3,   Casp10↑, 1,   cl‑Casp12↑, 1,   Casp3↑, 13,   cl‑Casp3↑, 4,   Casp6↑, 1,   Casp7↑, 1,   Casp8↓, 1,   Casp8↑, 5,   cl‑Casp8↑, 1,   Casp9↑, 8,   cl‑Casp9↑, 2,   Cyt‑c↑, 11,   Cyt‑c↝, 1,   Diablo↑, 2,   DR5↑, 2,   FADD↑, 1,   Fas↑, 3,   FasL↑, 2,   GSDME-N↑, 1,   hTERT/TERT↓, 1,   JNK↑, 2,   p‑JNK↑, 1,   MAPK↓, 2,   MAPK↑, 1,   Mcl-1↓, 4,   MDM2↓, 1,   Myc↓, 2,   NAIP↓, 1,   p27↑, 2,   p38↓, 1,   p‑p38↑, 2,   Pyro↑, 1,   survivin↓, 1,   Telomerase↓, 1,   TRAIL↑, 1,   TumCD↑, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 2,   p‑cJun↑, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 4,   eIF2α↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 4,   GRP78/BiP↑, 1,   HSP27↓, 1,   HSP27↑, 1,   HSP70/HSPA5↓, 2,   PERK↑, 1,   UPR↑, 2,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   Beclin-1↑, 3,   LC3B↑, 1,   LC3II↑, 2,   p62↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 4,   P53↑, 3,   PARP↑, 3,   cl‑PARP↑, 8,   PCNA↓, 1,   RAD51↓, 1,   TP53↓, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 4,   CDK4↓, 3,   cycA1/CCNA1↓, 2,   cycD1/CCND1↓, 3,   P21↑, 5,   Securin↓, 1,   TumCCA↑, 11,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 2,   EMT↓, 2,   ERK↓, 2,   ERK↑, 1,   p‑ERK↓, 1,   FOXO3↓, 1,   Gli1↓, 1,   GSK‐3β↑, 1,   p‑GSK‐3β↓, 1,   HDAC2↓, 1,   HDAC3↓, 1,   IGF-1↓, 1,   IGF-1R↓, 2,   IGF-1R↑, 1,   IGF-2↓, 1,   IGFBP3↑, 1,   mTOR↓, 4,   p‑mTOR↓, 1,   mTORC1↓, 1,   NOTCH↓, 1,   NOTCH3↓, 1,   PI3K↓, 6,   p‑PI3K↓, 1,   PTEN↑, 2,   Smo↓, 1,   STAT3↓, 1,   TCF↑, 1,   TRPM7↓, 1,   TumCG↓, 1,   Wnt↓, 2,   Wnt↑, 1,   Wnt/(β-catenin)↓, 1,  

Migration ⓘ

Akt2↓, 1,   Ca+2↑, 2,   E-cadherin↓, 1,   E-cadherin↑, 3,   Fibronectin↓, 2,   Ki-67↓, 1,   MET↓, 1,   MMP1↓, 1,   MMP2↓, 4,   MMP3↓, 1,   MMP7↓, 2,   MMP9↓, 3,   N-cadherin↓, 4,   Snail↓, 3,   TIMP1↑, 1,   TumCMig↓, 1,   TumCP↓, 6,   TumMeta↓, 1,   Twist↓, 1,   uPA↓, 3,   Vim↓, 4,   Zeb1↓, 1,   Zeb1↑, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   ATF4↓, 1,   ATF4↑, 2,   EGFR↓, 3,   eNOS↓, 1,   Hif1a↓, 4,   VEGF↓, 5,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IKKα↑, 1,   NF-kB↓, 6,   NF-kB↑, 1,   p65↓, 2,   PD-L1↑, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   BioAv↝, 1,   ChemoSen↑, 3,   eff↓, 3,   eff↑, 7,   eff↝, 1,   Half-Life↝, 1,   RadioS↑, 3,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

EGFR↓, 3,   hTERT/TERT↓, 1,   Ki-67↓, 1,   Myc↓, 2,   PD-L1↑, 1,   TP53↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   hepatoP↑, 1,   toxicity↓, 2,  
Total Targets: 214

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   Catalase↑, 1,   GSH↑, 2,   MDA↓, 1,   MPO↓, 1,   NRF2↑, 2,   ROS↓, 3,   SOD↑, 2,  

Core Metabolism/Glycolysis ⓘ

glucose↓, 1,   LDHA↑, 1,   LDL↓, 1,  

Cell Death ⓘ

BAX↓, 1,   Cyt‑c↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,  

Migration ⓘ

AntiAg↑, 1,   Ca+2?, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 4,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,  

Functional Outcomes ⓘ

cardioP↑, 2,   chemoP↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 4,  

Infection & Microbiome ⓘ

Bacteria↓, 1,  
Total Targets: 26

Scientific Paper Hit Count for: BAD, BCL2 associated agonist of cell death
4 Fisetin
2 Berberine
2 EGCG (Epigallocatechin Gallate)
1 Ashwagandha(Withaferin A)
1 immunotherapy
1 Betulinic acid
1 Carvacrol
1 Thymol-Thymus vulgaris
1 Curcumin
1 Citric Acid
1 Juglone
1 Luteolin
1 Magnolol
1 Oleuropein
1 HydroxyTyrosol
1 Propyl gallate
1 Piperine
1 Quercetin
1 Paclitaxel
1 Aflavin-3,3′-digallate
1 triptolide
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

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