EGFR Cancer Research Results

EGFR, Epidermal Growth Factor Receptor: Click to Expand ⟱
Source: HalifaxProj(inhibit) CGL-Driver
Type: Oncogene
EGFR (Epidermal growth factor receptor), which belongs to the tyrosine kinase receptor family (RTKs)
Epidermal Growth Factor Receptor (EGFR) is a cell surface protein that plays a crucial role in the regulation of cell growth, survival, proliferation, and differentiation. It is part of the ErbB family of receptors and is activated by binding to its ligands, such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α).

-plays a crucial role in regulating cell growth and division.

Many cancers exhibit overexpression of EGFR, which can lead to enhanced signaling and contribute to tumor growth and survival. This overexpression is often associated with aggressive tumor behavior and poor prognosis.
Scientific Papers found: Click to Expand⟱
5431- AG,    Advances in research on the anti-tumor mechanism of Astragalus polysaccharides
- Review, Var, NA
AntiTum↑, APS has been increasingly used in cancer therapy owing to its anti-tumor ability as it prevents the progression of prostate, liver, cervical, ovarian, and non-small-cell lung cancer by suppressing tumor cell growth and invasion and enhancing apoptosi
TumCG↓,
TumCI↓,
Apoptosis↑, after APS treatment, the apoptosis of HepG2 cells is accelerated (57).
Imm↑, APS enhances the sensitivity of tumors to antineoplastic agents and improves the body’s immunity
Bcl-2↓, Huang et al. proposed that APS induces H22 (a hepatocellular cancer [HCC] cell line) apoptosis by downregulating Bcl-2 and upregulating Bax expression (56).
BAX↑,
Wnt↓, downregulating the Wnt/β-catenin signaling pathway.
β-catenin/ZEB1↓,
TumCG↓, APS effectively inhibited the growth of MDA-MB-231 (a human breast cancer [BC] cell line) graft tumor (58)
miR-133a-3p↑, apoptosis rate of human osteosarcoma MG63 cells increased owing to the upregulation of miR-133a and inactivation of the JNK signaling pathways (71).
JNK↓,
Fas↑, Li and Shen found that APS can induce apoptosis by activating the Fas death receptor pathway.
P53↑, Zhang et al. showed that APS could activate p53 and p21 and inhibit the expression of Notch1 and Notch3 in vitro, ultimately inhibiting cell proliferation and promoting their apoptosis
P21↑,
NOTCH1↓,
NOTCH3↓,
TumCP↓,
TumCCA↑, Liu et al. found that APS induced the cell cycle of bladder cancer UM-UC-3 to stop in the G0/G1 phase, thus inhibiting its proliferation
GPx4↓, APS was found to reduce GPX4 expression, inhibit the activity of the light chain subunit SLC7A11 (xCT), and promote the formation of BECN1-xCT complex by activating AMPK/BECN1 signaling.
xCT↓,
AMPK↑,
Beclin-1↑,
NF-kB↓, APS could control the proliferation of lung cancer cells (A549 and NCI-H358 cells) by inhibiting the NF-κB signaling pathway (97)
EMT↓, APS treatment led to reduced EMT markers (vimentin, AXL) and MIF levels in cells.
Vim↓,
TumMeta↓, APS inhibits Lewis lung cancer growth and metastasis in mice by significantly reducing VEGF and EGFR expression in cancerous tissues
VEGF↓,
EGFR↓,
eff↑, Nano-drug delivery systems can increase efficiency and reduce toxicity
eff↑, Jiao et al. developed selenium nanoparticles modified with macromolecular weight APS and observed positive results in hepatoma treatment
MMP↓, Subsequent investigations revealed that APS can decrease the ΔΨm values and Bcl-2, p-PI3K, P-gp, and p-AKT levels while elevating Bax expression.
P-gp↓,
MMP9↓, downregulation of MMP-9 expression,
ChemoSen↑, Li et al. observed that APS could enhance the sensitivity of SKOV3 ovarian cancer cells to CDDP treatment by activating the mitochondrial apoptosis pathway and JNK1/2 signaling pathway
SIRT1↓, APS significantly suppressed SIRT1 and SREBP1 expression, decreased cholesterol and triglyceride levels in PC3 and DU145, and attenuated cell proliferation.
SREBP1↓,
TumAuto↑, APS can induce autophagy in colorectal cancer cells by inhibiting the PI3K/AKT/mTOR axis and the development of cancer cells.
PI3K↓,
mTOR↓,
Casp3↑, Shen found that APS elevated caspase-9, caspase-3, and Bax protein levels, decreased Bcl-2 protein expression, and inhibited CD133 and CD44 co-positive colon cancer stem cell proliferation time
Casp9↑,
CD133↓,
CD44↓,
CSCs↓,
QoL↑, QOL was significantly improved as indicated by the reduction in pain and improvement in appetite

5976- AgNPs,    Review on Harnessing Silver Nanoparticles for Therapeutic Innovations: A Comprehensive Review on Medical Applications, Safety, and Future Directions
- Review, Vit, NA
*Bacteria↓, strong antibacterial, anticancer, anti-inflammatory, and wound-healing properties.
AntiCan↑,
*Inflam↓,
*Wound Healing↑,
eff↑, Cytotoxic effects of anticancer drugs such as verapamil, cisplatin, carmustine, and methotrexate are improved by citrate-coated silver oxide NP
ChemoSen↑,
EGFR↓, silver (AgNPs), gold (AuNPs), and superparamagnetic iron oxide nanoparticles (SPIONPs) have shown the ability to interfere with EGFR
ROS↑, In MCF-7 breast cancer cells, AgNP induced ROS activated proteins, such as p53, Bax, and caspase-3, cause programmed cell death
P53↑,
BAX↑,
Casp3↑,
toxicity↝, AgNPs produce ionic silver and ROS that have antibacterial properties, but their non-specific absorption can harm healthy cells.

231- AL,    EGFR_Protein_for_Lung_Cancer_Therapy">Molecular Docking Studies with Garlic Phytochemical Constituents to Inhibit the Human EGFR Protein for Lung Cancer Therapy
- Analysis, Lung, NA
EGFR↓,
ROS↑, pro-oxidants in inflammatory conditions

3443- ALA,    Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention
- Review, Var, NA - Review, AD, NA
*antiOx↑, antioxidant potential and free radical scavenging activity.
*ROS↓,
*IronCh↑, Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E.
*cognitive↑, α-Lipoic acid enantiomers and its reduced form have antioxidant, cognitive, cardiovascular, detoxifying, anti-aging, dietary supplement, anti-cancer, neuroprotective, antimicrobial, and anti-inflammatory properties.
*cardioP↓,
AntiCan↑,
*neuroP↑,
*Inflam↓, α-Lipoic acid can reduce inflammatory markers in patients with heart disease
*BioAv↓, bioavailability in its pure form is low (approximately 30%).
*AntiAge↑, As a dietary supplements α-lipoic acid has become a common ingredient in regular products like anti-aging supplements and multivitamin formulations
*Half-Life↓, it has a half-life (t1/2) of 30 min to 1 h.
*BioAv↝, It should be stored in a cool, dark, and dry environment, at 0 °C for short-term storage (few days to weeks) and at − 20 °C for long-term storage (few months to years).
other↝, Remarkably, neither α-lipoic acid nor dihydrolipoic acid can scavenge hydrogen peroxide, possibly the most abundant second messenger ROS, in the absence of enzymatic catalysis.
EGFR↓, α-Lipoic acid inhibits cell proliferation via the epidermal growth factor receptor (EGFR) and the protein kinase B (PKB), also known as the Akt signaling, and induces apoptosis in human breast cancer cells
Akt↓,
ROS↓, α-Lipoic acid tramps the ROS followed by arrest in the G1 phase of the cell cycle and activates p27 (kip1)-dependent cell cycle arrest via changing of the ratio of the apoptotic-related protein Bax/Bcl-2
TumCCA↑,
p27↑,
PDH↑, α-Lipoic acid drives pyruvate dehydrogenase by downregulating aerobic glycolysis and activation of apoptosis in breast cancer cells, lactate production
Glycolysis↓,
ROS↑, HT-29 human colon cancer cells; It was concluded that α-lipoic acid induces apoptosis by a pro-oxidant mechanism triggered by an escalated uptake of mitochondrial substrates in oxidizable form
*eff↑, Several studies have found that combining α-lipoic acid and omega-3 fatty acids has a synergistic effect in slowing functional and cognitive decline in Alzheimer’s disease
*memory↑, α-lipoic acid inhibits brain weight loss, downregulates oxidative tissue damage resulting in neuronal cell loss, repairs memory and motor function,
*motorD↑,
*GutMicro↑, modulates the gut microbiota without reducing the microbial diversity (

297- ALA,    Insights on the Use of α-Lipoic Acid for Therapeutic Purposes
- Review, BC, SkBr3 - Review, neuroblastoma, SK-N-SH - Review, AD, NA
PDH↑, ALA is capable of activating pyruvate dehydrogenase in tumor cells.
TumCG↓, ALA also significantly inhibited tumor growth in mouse xenograft model using BCPAP and FTC-133 cells
ROS↑, ALA is able to generate ROS, which promote ALA-dependent cell death in lung cancer [75], breast cancer [76] and colon cancer
AMPK↑,
EGR4↓,
Half-Life↓, Data suggests that ALA has a short half-life and bioavailability (about 30%)
BioAv↝,
*GSH↑, Moreover, it is able to increase the glutathione levels inside the cells, that chelate and excrete a wide variety of toxins, especially toxic metals from the body
*IronCh↑, The existence of thiol groups in ALA is responsible for its metal chelating abilities [14,35].
*ROS↓, ALA exerts a direct impact in oxidative stress reduction
*antiOx↑, ALA is being referred as the universal antioxidant
*neuroP↑, ALA has neuroprotective effects on Aβ-mediated cytotoxicity
*Ach↑, ALA show anti-dementia or anti-AD properties by increasing acetylcholine (ACh) production through activation of choline acetyltransferase, which increases glucose absorption
*lipid-P↓, ALA has multiple and complex effects in this way, namely scavenging ROS, transition metal ions, increasing the levels of reduced glutathione [59,63], scavenging of lipid peroxidation products
*IL1β↓, ALA downregulated the levels of the inflammatory cytokines IL-1B and IL-6 in SK-N-BE human neuroblastoma cells
*IL6↓,
TumCP↓, ALA inhibited cell proliferation, [18F]-FDG uptake and lactate formation and increased apoptosis in neuroblastoma cell lines Kelly, SK-N-SH, Neuro-2a and in the breast cancer cell line SkBr3.
FDG↓,
Apoptosis↑,
AMPK↑, ALA suppressed thyroid cancer cell proliferation and growth through activation of AMPK and subsequent down-regulation of mTOR-S6 signaling pathway in BCPAP, HTH-83, CAL-62 and FTC-133 cells lines.
mTOR↓,
EGFR↓, ALA inhibited cell proliferation through Grb2-mediated EGFR down-regulation
TumCI↓, ALA inhibited metastatic breast cancer cells migration and invasion, partly through ERK1/2 and AKT signaling
TumCMig↓,
*memory↑, Alzheimer’s Disease: ALA led to a marked improvement in learning and memory retention
*BioAv↑, Since ALA is poorly soluble, lecithin has been used as an amphiphilic matrix to enhance its bioavailability.
*BioAv↝, ALA were found to be considerably higher in adults with mean age greater than 75 years as compared to young adults between the ages of 18 and 45 years.
*other↓, ALA treatment has been recently studied by some clinical trials to explain its efficacy in preventing miscarriage
*other↝, 1800 mg of ALA or placebo were administrated orally every day, except during the period 2 days before to 4 days after administration of each dose of platinum to avoid potential interference with platinum’s antitumor effects
*Half-Life↓, Data shows a short half-life and bioavailability of about 30% of ALA due to mechanisms involving hepatic degradation, reduced ALA solubility as well as instability in the stomach.
*BioAv↑, ALA bioavailability is greatly reduced after food intake and it has been recommended that ALA should be admitted at least 2 h after eating or if taken before; meal should be taken at least 30 min after ALA administration
*ChAT↑, ALA show anti-dementia or anti-AD properties by increasing acetylcholine (ACh) production through activation of choline acetyltransferase, which increases glucose absorption
*GlucoseCon↑,

5361- almon,    Abstract CT190: A multicenter, open-label, single-arm, phase II study: The third generation EGFR tyrosine kinase inhibitor almonertinib for pretreated EGFR T790M-positive locally advanced or metastatic non-small cell lung cancer (APOLLO)
- Trial, NSCLC, NA
EGFR↓, Almonertinib (HS-10296) is an oral, potent, high selective third generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) for sensitizing mutations and EGFR T790M mutation.
OS↑, Almonertinib demonstrated progression-free survival benefit in EGFR T790M positive NSCLC patients
Dose↝, received almonertinib 110 mg orally once daily until disease progression.

5359- almon,    Aumolertinib as adjuvant therapy in resected EGFR-mutated non-small-cell lung cancer (ARTS): a double-blind, multicentre, randomised, controlled, phase 3 trial
- Trial, NSCLC, NA
eff↑, Aumolertinib showed substantial clinical benefits as adjuvant therapy in Chinese patients with stage II–IIIB EGFR-mutated NSCLC.
EGFR↓,

5358- almon,    Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models
- vitro+vivo, NSCLC, NA
TumMeta↓, The results of this study show that almonertinib can significantly inhibit PC9 brain and spinal cord metastases.
BBB↑, Pharmacokinetic studies in mice revealed that almonertinib has good BBB penetration ability, whereas the metabolite HAS-719 does not easily penetrate the BBB.
EGFR↓, The molecular docking results showed that almonertinib can flexibly bind to small molecule pockets on the EGFR-T790 mutant protein with a better geometrical match.

5357- almon,    AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or MetastaticNon-Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations
- Trial, NSCLC, NA
EGFR↓, Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.
eff↝, Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively;
OS↑, see figure 1

2640- Api,    Apigenin: A Promising Molecule for Cancer Prevention
- Review, Var, NA
chemoPv↑, considerable potential for apigenin to be developed as a cancer chemopreventive agent.
ITGB4↓, apigenin inhibits hepatocyte growth factor-induced MDA-MB-231 cells invasiveness and metastasis by blocking Akt, ERK, and JNK phosphorylation and also inhibits clustering of β-4-integrin function at actin rich adhesive site
TumCI↓,
TumMeta↓,
Akt↓,
ERK↓,
p‑JNK↓,
*Inflam↓, The anti-inflammatory properties of apigenin are evident in studies that have shown suppression of LPS-induced cyclooxygenase-2 and nitric oxide synthase-2 activity and expression in mouse macrophages
*PKCδ↓, Apigenin has been reported to inhibit protein kinase C activity, mitogen activated protein kinase (MAPK), transformation of C3HI mouse embryonic fibroblasts and the downstream oncogenes in v-Ha-ras-transformed NIH3T3 cells (43, 44).
*MAPK↓,
EGFR↓, Apigenin treatment has been shown to decrease the levels of phosphorylated EGFR tyrosine kinase and of other MAPK and their nuclear substrate c-myc, which causes apoptosis in anaplastic thyroid cancer cells
CK2↓, apigenin has been shown to inhibit the expression of casein kinase (CK)-2 in both human prostate and breast cancer cells
TumCCA↑, apigenin induces a reversible G2/M and G0/G1 arrest by inhibiting p34 (cdc2) kinase activity, accompanied by increased p53 protein stability
CDK1↓, inhibiting p34 (cdc2) kinase activity
P53↓,
P21↑, Apigenin has also been shown to induce WAF1/p21 levels resulting in cell cycle arrest and apoptosis in androgen-responsive human prostate cancer
Bax:Bcl2↑, Apigenin treatment has been shown to alter the Bax/Bcl-2 ratio in favor of apoptosis, associated with release of cytochrome c and induction of Apaf-1, which leads to caspase activation and PARP-cleavage
Cyt‑c↑,
APAF1↑,
Casp↑,
cl‑PARP↑,
VEGF↓, xposure of endothelial cells to apigenin results in suppression of the expression of VEGF, an important factor in angiogenesis via degradation of HIF-1α protein
Hif1a↓,
IGF-1↓, oral administration of apigenin suppresses the levels of IGF-I in prostate tumor xenografts and increases levels of IGFBP-3, a binding protein that sequesters IGF-I in vascular circulation
IGFBP3↑,
E-cadherin↑, apigenin exposure to human prostate carcinoma DU145 cells caused increase in protein levels of E-cadherin and inhibited nuclear translocation of β-catenin and its retention to the cytoplasm
β-catenin/ZEB1↓,
HSPs↓, targets of apigenin include heat shock proteins (61), telomerase (68), fatty acid synthase (69), matrix metalloproteinases (70), and aryl hydrocarbon receptor activity (71) HER2/neu (72), casein kinase 2 alpha
Telomerase↓,
FASN↓,
MMPs↓,
HER2/EBBR2↓,
CK2↓,
eff↑, The combination of sulforaphane and apigenin resulted in a synergistic induction of UGT1A1
AntiAg↑, Apigenin inhibit platelet function through several mechanisms including blockade of TxA
eff↑, ex vivo anti-platelet effect of aspirin in the presence of apigenin, which encourages the idea of the combined use of aspirin and apigenin in patients in which aspirin fails to properly suppress the TxA
FAK↓, Apigenin inhibits expression of focal adhesion kinase (FAK), migration and invasion of human ovarian cancer A2780 cells.
ROS↑, Apigenin generates reactive oxygen species, causes loss of mitochondrial Bcl-2 expression, increases mitochondrial permeability, causes cytochrome C release, and induces cleavage of caspase 3, 7, 8, and 9 and the concomitant cleavage of the inhibitor
Bcl-2↓,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp7↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑IAP2↑,
AR↓, significant decrease in AR protein expression along with a decrease in intracellular and secreted forms of PSA. Apigenin treatment of LNCaP cells
PSA↓,
p‑pRB↓, apigenin inhibited hyperphosphorylation of the pRb protein
p‑GSK‐3β↓, Inhibition of p-Akt by apigenin resulted in decreased phosphorylation of GSK-3beta.
CDK4↓, both flavonoids exhibited cell growth inhibitory effects which were due to cell cycle arrest and downregulation of the expression of CDK4
ChemoSen↑, Combination therapy of gemcitabine and apigenin enhanced anti-tumor efficacy in pancreatic cancer cells (MiaPaca-2, AsPC-1)
Ca+2↑, apigenin in neuroblastoma SH-SY5Y cells resulted in increased apoptosis, which was associated with increases in intracellular free [Ca(2+)] and Bax:Bcl-2 ratio, mitochondrial release of cytochrome c and activation of caspase-9, calpain, caspase-3,12
cal2↑,

416- Api,    In Vitro and In Vivo Anti-tumoral Effects of the Flavonoid Apigenin in Malignant Mesothelioma
- vitro+vivo, NA, NA
Bax:Bcl2↑,
P53↑,
ROS↑,
Casp9↑,
Casp8↑,
cl‑PARP1↑, cleavage
p‑ERK⇅, Here, we demonstrated that API treatment was able to increase ERK1/2 phosphorylation in MM-B1, H-Meso-1, and #40a cells while induced a decrease of ERK1/2 activation in MM-F1 cells.
p‑JNK↓,
p‑p38↑,
p‑Akt↓,
cJun↓,
NF-kB↓,
EGFR↓,
TumCCA↑, increase of the percentage of cells in subG1 phase

574- ART/DHA,    Dihydroartemisinin suppresses glioma proliferation and invasion via inhibition of the ADAM17 pathway
TumCP↓,
TumCMig↓,
TumCI↓,
MMP17↓,
p‑EGFR↓,
p‑Akt↓,

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↓,

557- ART/DHA,    Artemisinin and Its Derivatives in Cancer Care
- Review, Var, NA
*BioAv↓, with High fat and high calorie meals
*BioAv↑, DHA dihydroartemisinin have improved bioavailability
Apoptosis↑,
EGFR↓,
CD31↓,
Ki-67↓,
P53↓,
TfR1/CD71↑,
P-gp↓, many artemisinin derivatives act as P-gp inhibitors
PD-1↝, Caution when used with mmunotherapy (PD1/PDL1 inhibitors)

1358- Ash,    Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms
- Review, Var, NA
TumCCA↑,
Apoptosis↑,
TumAuto↑,
Ferroptosis↑,
TumCP↓,
CSCs↓,
TumMeta↓,
EMT↓,
angioG↓,
Vim↓,
HSP90↓,
annexin II↓, annexin II proteins directly bind to WA
m-FAM72A↓,
BCR-ABL↓,
Mortalin↓,
NRF2↓,
cMYB↓,
ROS↑, WA inhibits proliferation through ROS-mediated intrinsic apoptosis
ChemoSen↑, WA and cisplatin, WA produced ROS, while cisplatin caused DNA damage, suggesting that lower doses of cisplatin combined with suboptimal doses of WA could achieve the same effect
eff↑, sulforaphane and WA showed synergistic effects on epigenetic modifiers and cell proliferation in breast cancer cells
ChemoSen↑, WA and sorafenib caused G2/M arrest in anaplastic and papillary thyroid cancer cells
ChemoSen↑, combination of WA and 5-FU executed PERK axis-mediated endoplasmic reticulum (ER) stress-induced autophagy and apoptosis
eff↑, WA and carnosol also exhibit a synergistic effect on pancreatic cancer
*BioAv↓, Saurabh by Saurabh et al and Tianming et al reported oral bioavailability values 1.8% and 32.4 ± 4.8%, respectively, in male rats.
ROCK1↓, In another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angi
TumCI↓,
Sp1/3/4↓, Furthermore, WA exerts potent anti-angiogenic activity in vivo.174 In the Ehrlich ascites tumor model, WA exerts its anti-angiogenic activity by reducing the binding of the transcription factor specificity protein 1 (Sp1) to VEGF
VEGF↓, n another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angio
Hif1a↓, Furthermore, WA suppresses the AK4-HIF-1α signaling axis and acts as a potent antimetastatic agent in lung cancer.Citation79
EGFR↓, WA synergistically inhibited wild-type epidermal growth factor receptor (EGFR) lung cancer cell viability

4805- ASTX,    Astaxanthin promotes apoptosis by suppressing growth signaling pathways in HT-29 colorectal cancer cells
- in-vitro, Colon, HT29
TumCP↓, ATX exhibited significant antiproliferative and pro-apoptotic effects on HT-29 cells, with an IC50 value of 10.98 µM at 24 h
Casp3↑, reatment with ATX (10.98 µM) led to a marked increase in caspase-3 expression and a significant reduction in EGFR levels.
EGFR↓,
HER2/EBBR2↓, Additionally, HER2, ERK1 and ERK2 levels were significantly downregulated
ERK↓,
Apoptosis↑, analysis revealed a significant increase in apoptotic cell populations following ATX treatment, compared to the control group.

5363- AV,    Exploring the mechanism of aloe-emodin in the treatment of liver cancer through network pharmacology and cell experiments
- Study, HCC, NA
AKT1↓, The involvement of AKT1 and EGFR, as well as the key target of the PI3K-AKT signaling pathway, indicated the importance of this signaling pathway in the treatment of HCC using AE.
EGFR↓,
PI3K↓, The downregulation of EGFR, PI3KR1, AKT1, and BCL2 in mRNA expression and PI3KR1, AKT,p-AKT in protein expression confirmed our hypothesis.
Bcl-2↓,
TumCG↓, AE inhibited hepatic cancer cell growth in vitro
Apoptosis↑, AE induced apoptosis of HCC cells

2021- BBR,    Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways
- Review, NA, NA
*antiOx?, Berberine has been noted as a potential therapeutic candidate for liver fibrosis due to its antioxidant and anti-inflammatory activities
*Inflam↓,
Apoptosis↑, Apoptosis induced by berberine in liver cancer cells caused cell cycle arrest at the M/G1 phase and increased the Bax expression
TumCCA↑,
BAX↑,
eff↑, mixture of curcumin and berberine effectively decreases growth in breast cancer cell lines
VEGF↓, berberine also prevented the expression of VEGF
PI3K↓, berberine plays an important role in cancer management through inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Telomerase↓, Berberine decreased the telomerase activity and level of the colorectal cancer cell line,
β-catenin/ZEB1↓, berberine and its derivatives have the ability to inhibit β-catenin/Wnt signaling in tumorigenesis
Wnt↓,
EGFR↓, berberine treatment decreased cell proliferation and epidermal growth factor receptor expression levels in the xenograft model.
AP-1↓, Berberine efficiently targets both the host and the viral factors accountable for cervical cancer development via inhibition of activating protein-1
NF-kB↓, berberine inhibited lung cancer cell growth by concurrently targeting NF-κB/COX-2, PI3K/AKT, and cytochrome-c/caspase signaling pathways
COX2↑,
NRF2↓, Berberine suppresses the Nrf2 signaling-related protein expression in HepG2 and Huh7 cells,
RadioS↑, suggesting that berberine supports radiosensitivity through suppressing the Nrf2 signaling pathway in hepatocellular carcinoma cells
STAT3↓, regulating the JAK–STAT3 signaling pathway
ERK↓, berberine prevented the metastatic potential of melanoma cells via a reduction in ERK activity, and the protein levels of cyclooxygenase-2 by a berberine-caused AMPK activation
AR↓, Berberine reduced the androgen receptor transcriptional activity
ROS↑, In a study on renal cancer, berberine raised the levels of autophagy and reactive oxygen species in human renal tubular epithelial cells derived from the normal kidney HK-2 cell line, in addition to human cell lines ACHN and 786-O cell line.
eff↑, berberine showed a greater apoptotic effect than gemcitabine in cancer cells
selectivity↑, After berberine treatment, it was noticed that berberine showed privileged selectivity towards cancer cells as compared to normal ones.
selectivity↑, expression of caspase-1 and its downstream target Interleukin-1β (IL-1β) was higher in osteosarcoma cells as compared to normal cells
BioAv↓, several studies have been undertaken to overcome the difficulties of low absorption and poor bioavailability through nanotechnology-based strategies.
DNMT1↓, In human multiple melanoma cell U266, berberine can inhibit the expression of DNMT1 and DNMT3B, which leads to hypomethylation of TP53 by altering the DNA methylation level and the p53-dependent signal pathway
cMyc↓, Moreover, berberine suppresses SLC1A5, Na+ dependent transporter expression through preventing c-Myc

2694- BBR,    Berberine down-regulates IL-8 expression through inhibition of the EGFR/MEK/ERK pathway in triple-negative breast cancer cells
- in-vitro, BC, NA
IL8↓, BBR dramatically suppresses IL-8 expression.
TumCI↓, BBR also inhibited cell invasiveness
EGFR↓, BBR down-regulates EGFR protein expression and dose-dependently inhibits MEK and ERK phosphorylation.
MEK↓,
ERK↓,
TGF-β1↓, BBR inhibits the tumorigenic and angiogenic properties of TNBC cells by inhibiting TGF-β1 expression and VEGF secretion (
VEGF↓,

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↑,

5633- BCA,    Mechanisms Behind the Pharmacological Application of Biochanin-A: A review
- Review, Var, NA - Review, AD, NA
*AntiDiabetic↑, Through modulating oxidative stress, SIRT-1 expression, PPAR gamma receptors, and other multiple mechanisms biochanin-A produces anti-diabetic action.
*neuroP↑, Biochanin-A has been shown to have a potential neuroprotective impact by modulating multiple critical neurological pathways.
*toxicity↓, Unlike chemical agents such as chemotherapeutic agents, isoflavones have shown zero toxicity to humans
*CYP19↓, Biochanin-A inhibits CYP19 and negatively affects the synthesis of oestrogen in the body which enhances the anti-oestrogenic property in hormone-influenced cancer such as prostate cancer and breast cancer
p‑Akt↓, Biochanin-A inhibits Akt phosphorylation thereby downregulates mTOR signals and disrupts the cell cycle.
mTOR↓,
TumCCA↑,
P21↑, Biochanin-A cause apoptosis in lung cancer by increasing p21, caspase-3, and Bcl-2 levels. It lowers E-cadherin and blocks metastasis.
Casp3↑,
Bcl-2↑,
Apoptosis↑,
E-cadherin↓,
TumMeta↓,
eff↑, The synergism of biochanin-A with 5-fluorouracil evidenced in Caco-2 and HCT-116 cell lines indicates the modulatory influence of biochanin-A in colon cancer treatment.
GSK‐3β↓, It blocked the “Akt and GSK3β phosphorylation and boosted the degradation of β-catenin” ( Mahmoud et al., 2017).
β-catenin/ZEB1↓,
RadioS↑, Biochanin-A when combined with gamma radiation on HT29 cells, which is resistant to radiation, had revealed a reduction in cell proliferation.
ROS↑, Raised levels of ROS, lipid peroxidation, MMP, caspase-3 have been observed more in the treatment group with significant apoptosis
Casp1↑,
MMP2↓, biochanin-A influenced the tumour invasion capacity by lowering matrix-degrading enzymes (MMP 2 and MMP 9) tested in U87MG cells
MMP9↓,
EGFR↓, Biochanin-A by lowering EGFR, p-ERK (Extracellular signal related kinases), p-AKT (Protein kinase-B), c-myc, and MT-MMP1 (Membrane type matrix metalloproteinase) activation, inhibited cell survival.
ChemoSen↑, Biochanin-A synergistically improved temozolomide anti-cancer ability in GBM
PI3K↓, Cell signalling pathways MAP kinase, PI3 kinase, mTOR, matrix metalloproteases, hypoxia-inducible factor, and VEGF were inhibited by biochanin-A, making it suitable in treating GBM
MMPs↓,
Hif1a↓,
VEGF↓,
*ROS↓, anti-diabetic mechanism of biochanin-A is by decreasing oxidative stress
*Obesity↓, strongly suggest that biochanin-A has therapeutic potential in the treatment of obesity and the prevention of cardiovascular disease
*cardioP↑,
*NRF2↑, Biochanin-A up-regulated the Nrf-2 pathway while suppressing the NF-κB cascade,
*NF-kB↓, By activating the Nrf-2 pathway and inhibiting NF-κB activation, biochanin-A may reduce obesity and its related cardiomyopathy by decreasing oxidative stress and inflammation
*Inflam↓,
*lipid-P↓, cardio-protective effects by controlling lipid peroxidation
*hepatoP↑, biochanin-A influence the elevated hepatic enzyme level, such as AST, ALP, ALT, bilirubin, etc., and found to be a promising molecule in hepatotoxicity models
*AST↓,
*ALP↓,
*Bacteria↓, The results indicate that biochanin-A may be an effective alternate to antibiotics for alleviating SARA in cattles
*neuroP↑, the neuroprotective effects of biochanin-A might be attributed to the activation of the Nrf2 pathway and suppression of the NF-κB pathway
*SOD↑, Biochanin-A reduced oxidative stress in the brain by augmenting SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase) and repressing MDA (malondialdehyde) levels.
*GPx↑,
*AChE↓, Acetylcholinesterase activity was found decreased in a dose-reliant manner amongst biochanin-A treated animals
*BACE↓, Biochanin-A non-competitively inhibited BACE1 with an IC 50 value of 28 μM.
*memory↑, estore learning and memory deficits in ovariectomized (OVX) rats.
*BioAv↓, The bioavailability of biochanin-A is poor.

2736- BetA,  Chemo,    Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis
- Review, Var, NA
chemoPv↑, reviews about cancer chemopreventive role of betulinic acid against wide variety of cancers [18,19,20,21].
p‑STAT3↓, betulinic acid reduced the levels of p-STAT3 in tumor tissues derived from KB cells
JAK1↓, Betulinic acid exerted inhibitory effects on the constitutive phosphorylation of JAK1 and JAK2
JAK2↓,
VEGF↓, betulinic acid mediated inhibition of VEGF
EGFR↓, evaluation of betulinic acid as a next-generation EGFR inhibitor
Cyt‑c↑, release of SMAC/DIABLO and cytochrome c from mitochondria in SHEP neuroblastoma cells
Diablo↑,
AMPK↑, Betulinic acid induced activation of AMPK and consequently reduced the activation of mTOR.
mTOR↓,
Sp1/3/4↓, Betulinic acid significantly reduced the quantities of Sp1, Sp3 and Sp4 in the tissues of the tumors derived from RKO cells
DNAdam↑, Betulinic acid efficiently triggered DNA damage (γH2AX) and apoptosis (caspase-3 and p53 phosphorylation) in temozolomide-sensitive and temozolomide-resistant glioblastoma cells.
Gli1↓, Betulinic acid effectively reduced GLI1, GLI2 and PTCH1 in RMS-13 cells.
GLI2↓,
PTCH1↓,
MMP2↓, betulinic acid exerted inhibitory effects on MMP-2 and MMP-9 in HepG2 cells.
MMP9↓,
miR-21↓, Collectively, p53 increased miR-21 levels and inhibited SOD2 levels, leading to significant increase in the accumulation of ROS levels and apoptotic cell death.
SOD2↓,
ROS↑,
Apoptosis↑,

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.

5729- BF,    Bufalin: a potential drug for regulating EGFR-TKIs resistance in lung cancer via the EGFR-PI3K/Akt-mTOR signaling
- in-vitro, Lung, NA
TumCCA↑, Bufalin and gefitinib could control the cell cycle, induce apoptosis, and impede H1975 cell development and growth.
Apoptosis↑,
TumCG↓,
EGFR↓, bufalin and gefitinib inhibited the growth of lung cancer tumor and decreased the expression of proteins pertinent to the EGFR-PI3K/Akt-mTOR pathway, including EGFR, Akt, mTOR, and p70S6K.
PI3K↓,
Akt↓,
mTOR↓,
P70S6K↓,

5728- BF,    Effects of bufalin on the proliferation of human lung cancer cells and its molecular mechanisms of action
- in-vitro, Lung, A549
TumCP↓, we have demonstrated that bufalin suppressed the proliferation of human NSCLC A549 cell line in time- and dose-dependent manners.
Apoptosis↑, Bufalin induced the apoptosis and cell cycle arrest by affecting the protein expressions of Bcl-2/Bax, cytochrome c, caspase-3, PARP, p53, p21WAF1, cyclinD1, and COX-2 in A549 cells.
TumCCA↑,
Bcl-2↝,
BAX↝,
Cyt‑c↝,
Casp3↝,
PARP↝,
P21↝,
cycD1/CCND1↝,
COX2↝,
p‑VEGFR2↓, bufalin reduced the protein levels of receptor expressions and/or phosphorylation of VEGFR1, VEGFR2, EGFR and/or c-Met in A549 cells.
EGFR↓,
Akt↓, bufalin inhibited the protein expressions and phosphorylation of Akt, NF-κB, p44/42 MAPK (ERK1/2) and p38 MAPK in A549 cells.
NF-kB↓,
p44↓,

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↓,

5686- BJ,  BRU,    A review of Brucea javanica: metabolites, pharmacology and clinical application
- Review, Var, NA
AntiTum↑, Notably, multiple metabolites in BJ demonstrate anti-tumor effects through various signaling pathways
other↝, well-known metabolites such as Brusatol and Bruceine D.
ChemoSen↑, Multiple clinical studies have demonstrated that the co-administration of BJ with other pharmacological agents in individuals with cancer can enhance therapeutic efficacy, improve patients’ quality of life, and mitigate adverse reactions
QoL↑,
chemoP↑,
*Inflam↓, Brusatol (Zhou et al., 2018) has been shown to reduce inflammation in RAW264.7 cells
NF-kB↓, nhibition of NF-ΚB and ras homolog gene families, member A/rho-associated kinase (RhoA/ROCK) signaling pathways.
TumCP↓, Brusatol has exhibited notable effects in inhibiting proliferation, invasion, and metastasis in a murine model of liver transplantation tumor in humans.
TumCI↓,
TumMeta↓,
Hif1a↓, In colorectal cancer, Brusatol functions by facilitating the degradation process of hypoxia-inducible factor-1 (HIF-1α) (Oh et al., 2017), mediated by prolyl hydroxylase (PHD), while concurrently suppressing NRF2
NRF2↓,
STAT3↓, impede the proliferation and migration of osteosarcoma cells through the inhibition of the STAT3 signaling pathway.
COX2↓, BJO (Lou et al., 2010) induced apoptosis of T24 bladder cancer cells, possibly by upregulating caspase-3 and caspase-9 expression by activating the caspase pathway and inhibiting the NF-ΚB and Cyclooxygenase-2 (COX-2).
Casp3↑,
Casp9↑,
ROS↑, Figure 10
EGFR↓,
NRF2↑, brusatol and dehydrobruceine B (DHB) effectively increased the concentration of reactive oxygen species (ROS) by activating the NRF2 pathway

3525- Bor,    Synthesis of DNA-Boron Cluster Composites and Assembly into Functional Nanoparticles with Dual, Anti-EGFR, and Anti-c-MYC Oncogene Silencing Activity
- in-vitro, PC, PANC1
EGFR↓, The nanoparticles exhibited notable silencing efficiency in vitro in a pancreatic carcinoma cell line PANC-1 toward EGFR and c-Myc genes at the mRNA level, and a significant efficiency at the protein level.
cMyc↓,

5691- BRU,    Brusatol Inhibits Proliferation, Migration, and Invasion of Nonsmall Cell Lung Cancer PC-9 Cells
- in-vitro, Lung, PC9 - in-vitro, Lung, H1975
TumCP↓, brusatol suppressed PC-9 cell proliferation, migration, and invasion, as well as induced apoptosis,
TumCMig↓,
TumCI↓,
Apoptosis↑,
EGFR↓, downregulation of epidermal growth factor receptor (EGFR), β-catenin, Akt, and STAT3
β-catenin/ZEB1↓,
Akt↓,
STAT3↓,
TumMeta↓, inhibiting the proliferative capacity and metastatic potential of PC-9 cells.
ChemoSen↑, Ren et al. found that brusatol enhanced patient sensitivity to chemotherapeutics by inhibiting the cellular defense mechanism mediated by nuclear factor (erythroid-derived 2)-like 2 protein (Nrf2), which promoted the degradation of Nrf2
NRF2↓,
Akt↓, Brusatol also induced cancer cell apoptosis by inhibiting the Akt/mTOR pathway.[5]
mTOR↓,

5699- BRU,  BJ,    Identification of the Brucea javanica Constituent Brusatol as a EGFR-Tyrosine Kinase Inhibitor in a Cell-Free Assay
- in-vitro, Lung, A549
EGFR↓, brusatol inhibits EGFR-TK
ChemoSen↑, is administered to cancer patients in combination with chemotherapy in the form of two patented galenic preparations, i.e., BJO emulsion injection and BJO soft capsule.5
NRF2↓, brusatol, with the inhibition of Nrf2 as the most evident
STAT3↓, inhibition of STAT3,16,29,37 PI3K/Akt/mTOR,18,22,38,39 RhoA/ROCK,20 HIF1α,27,40 and Skp1
PI3K↓,
Akt↓,
mTOR↓,
ROCK1↓,
Hif1a↓,

2016- CAP,    Capsaicin binds the N-terminus of Hsp90, induces lysosomal degradation of Hsp70, and enhances the anti-tumor effects of 17-AAG (Tanespimycin)
HSP90↓, Here, we investigated the mechanism by which capsaicin inhibits Hsp90
ATPase↓, capsaicin binds to the N-terminus of Hsp90 and inhibits its ATPase activity
eff↑, Combined treatments of capsaicin and the Hsp90 inhibitor 17-AAG improved the anti-tumor efficacy of 17-AAG in cell culture
HSP70/HSPA5↓, capsaicin triggers the lysosomal degradation of Hsp70 in various cancer cell lines
other↝, The mechanism by which capsaicin induces apoptosis in cancer cells is not well understood, but it appears to be independent of the TRPV1 receptor as neither capsazepine, a TRPV1 antagonist, nor intracellular Ca2+ chelators have been found to inhibit
NF-kB↓, capsaicin can block the activity of many oncogenic signaling proteins including NF-κB, ER, EGFR/HER2, CDK4, Src, VEGF, and PI3K/Akt, among others.
EGFR↓,
CDK4↓,
Src↓,
VEGF↓,
PI3K↓,
Akt↓,

5767- CAPE,    Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer
- Review, Oral, NA
TumCP↓, CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells.
tumCV↓,
TumMeta↓,
Akt↓, CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2).
NF-kB↓,
MMPs↓,
EGFR↓,
COX2↓,
TumCCA?, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells.

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.

5970- CET,    Cetuximab
- Review, CRC, NA - Review, HNSCC, NA
EGFR↓, Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor with the following FDA-approved indications: colorectal cancer, metastatic, KRAS wild-type (without mutation), and head and neck cancer (squamous cell).
OS↑, Colorectal cancer, metastatic, KRAS wild-type (without mutation) - Cetuximab improves both overall survival and progression-free survival and preserves quality-of-life measures for patients with colorectal cancer
QoL↑,
Dose↝, administration of the drug is via IV infusion with a loading dose lasting over 2 hours, weekly maintenance dose over 1 hour.

5968- CET,    Cetuximab as a Key Partner in Personalized Targeted Therapy for Metastatic Colorectal Cancer
- in-vitro, CRC, NA
eff↑, Combining cetuximab with immunotherapy and other targeted agents further expands the therapeutic landscape, offering renewed hope for mCRC patients who face the development of resistance to conventional therapies.
Half-Life↑, Pharmacokinetic differences include cetuximab’s non-linear clearance and longer half-life, while panitumumab exhibits both linear and non-linear clearance mechanisms and a shorter half-life [23].
Half-Life↑, These studies revealed that clearance from the bloodstream was relatively slow, with a median half-life of 7 days
EGFR↓, Cetuximab also aids in downregulating EGFR-dependent signaling by promoting the internalization of EGFR
OS↑, Cetuximab improved OS and PFS compared with best supportive care (BSC), while maintaining quality of life [
QoL↑,
eff↑, The BEACON trial illustrated that the combination of BRAF inhibition and anti-EGFR therapy using cetuximab yielded better results compared with irinotecan-based chemotherapy in refractory BRAF V600E mCRC patients.
KRAS↓, nhibition of KRAS G12C and Cetuximab

6026- CGA,    Chlorogenic Acid: The Conceivable Chemosensitizer Leading to Cancer Growth Suppression
- Review, Var, NA
ChemoSen↑, This article will elaborate the potency of CGA as a chemosensitizer in suppressing tumor growth through a metabolic pathway.
AMPK↑, AMPK pathway is the main cell metabolic pathway that is activated by CGA in some studies.
EGFR↓, Moreover, CGA inhibited EGFR/PI3K/mTOR, HIF, VEGF pathways and MAPK/ERK pathway that may suppress tumor cell growth.
PI3K↓,
mTOR↓,
Hif1a↓, CGA Inhibits HIF-1α/AKT Pathway
VEGF↓,
MAPK↓,
ERK↓,
DNAdam↑, CGA induced intracellular DNA damage and topoisomerase I- and II-DNA complexes formation that plays a key role in apoptosis.
TOP1↓, Topoisomerase inhibitor, known as cancer killer drug, works by inducing topoisomerase-mediated DNA damage
TOP2↓,
Apoptosis↑,
*BioAv↝, Around 70% of CGA is absorbed in small intestine and colon. CGA is relatively stable in saliva and gastric acid.
*Half-Life↓, most circulating CGA is eliminated quickly from the circulatory system with half-time of 0.3 to 1.9 hours and Tmax of 0.6 to 1 hour.

2785- CHr,    Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin
- Review, Var, NA
*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,

136- CUR,  docx,    Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
Bcl-2↓, combined treatment with curcumin with docetaxel down-regulates the expression of the anti-apoptotic proteins BCL-2, BCL-XL and MCL-1 in DU145 and PC3 cells
Bcl-xL↓,
Mcl-1↓,
BAX↑, Whereas, the expression of the pro-apoptotic markers BAK and BID were significantly up-regulated in curcumin with docetaxel treated group compared to curcumin and docetaxel-treated group alone
BID↑,
PARP↑, combined treatment with curcumin and docetaxel in DU145 and PC3 cells enhanced proteolysis of PARP compared
NF-kB↓, Curcumin blocks NF-κB activation in docetaxel-treated PCa cells
CDK1↓, treatment of curcumin and docetaxel significantly reduced the expression of the proliferation marker CDK-1 and inflammatory marker COX-2
COX2↓,
RTK-RAS↓,
PI3K/Akt↓, combined treatment of curcumin and docetaxel reduced the expression of PI3K, phospho-AKT, EGFR and HER2 in both DU145 and PC3 cells
EGFR↓,
HER2/EBBR2↓, docetaxel in combination with curcumin down-regulates the expression of HER2 and EGFR resulting inhibition of the expression of PI3K kinase and phospho-AKT
P53↑,
ChemoSen↑, The combined treatment of curcumin and docetaxel inhibited the proliferation and induced apoptosis significantly higher than the curcumin and docetaxel-treated group alone.

13- CUR,    Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action
- Review, BC, NA
P53↑, upregulated other targets including p53, death receptor (DR-5), JN-kinase, Nrf-2, and peroxisome proliferator-activated receptor γ (PPARγ) factors
DR5↑,
JNK↑,
NRF2↑,
PPARγ↑,
HER2/EBBR2↓, (Her-2, IR, ER-a, and Fas receptor)
IR↓,
ER(estro)↓,
Fas↑,
PDGF↓, (PDGF, TGF, FGF, and EGF)
TGF-β↓,
FGF↓,
EGFR↓,
JAK↓,
PAK↓,
MAPK↓,
ATPase↓, (ATPase, COX-2, and matrix metalloproteinase enzyme [MMP])
COX2↓,
MMPs↓,
IL1↓, inflammatory cytokines (IL-1, IL-2, IL-5, IL-6, IL-8, IL-12, and IL-18)
IL2↓,
IL5↓,
IL6↓,
IL8↓,
IL12↓,
IL18↓,
NF-kB↓,
NOTCH1↓,
STAT1↓,
STAT4↓,
STAT5↓,
STAT3↓,

484- CUR,  PDT,    Low concentrations of curcumin induce growth arrest and apoptosis in skin keratinocytes only in combination with UVA or visible light
- in-vitro, Melanoma, NA
Cyt‑c↑, release of cytochrome c from mitochondria
Casp9↑,
Casp8↑,
NF-kB↓,
EGFR↓,

452- CUR,    Curcumin downregulates the PI3K-AKT-mTOR pathway and inhibits growth and progression in head and neck cancer cells
- vitro+vivo, HNSCC, SCC9 - vitro+vivo, HNSCC, FaDu - vitro+vivo, HNSCC, HaCaT
TumCCA↑, arrested cell cycle at phase G2 /M
PI3k/Akt/mTOR↓,
Casp3↑,
EGFR↓, 0.18 fold
EGF↑, Curcumin induced a noticeable increase in the expression of EGF (11.3-fold change)
PRKCG↑, 13.2 fold
p‑Akt↓,
p‑mTOR↓,
RPS6KA1↓, 0.17 fold
EIF4E↓, 0.18 fold
proCasp3↓,

4671- CUR,    Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy
- in-vitro, CRC, NA
CSCs↓, Intriguingly, curcumin and its analogues have also recently been shown to be effective in lowering tumour recurrence by targeting the CSC population, hence inhibiting tumour growth.
TumCG↓,
ChemoSen↑, curcumin could play a role as chemosensitiser whereby the colorectal CSCs are now sensitised towards the anti-cancer therapy,
Wnt↓, Three major signaling pathways in which curcumin plays a pivotal role in CSC self-renewal behavior are the Wnt/β-catenin, Sonic Hedgehog (SHH), and Notch pathways
β-catenin/ZEB1↓,
Shh↓,
NOTCH↓,
DNMT1↓, Figure 1
STAT3↓,
NF-kB↓,
EGFR↓,
IGFR↓,
TumCCA↓,
cl‑PARP↑,
BAX↑,
ECM/TCF↓,

2814- CUR,    Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management
- Review, Var, NA
*BioAv↓, curcumin’s practical application in medicine is hindered by its limited bioavailability. low solubility in water and rapid breakdown in the body
*Inflam↓, anti-inflammatory, antioxidant, and potential anticancer abilities
*antiOx↑,
AntiCan↑,
CK2↓, Curcumin exhibited an IC50 of 2.38 ± 0.15 μM against CK2α
GSK‐3β↓, roles of GSK3β and how they are suppressed by curcumin
EGFR↓, roles of EGFR and how it is inhibited by the curcumin analog, 3a
TOP1↓, unwinding of DNA supercoils by Topo I and Topo II and their inhibition by cyclocurcumin
TOP2↓,
NF-kB↓, The activation of NF-kB signaling and the inhibition of NF-kB’s activity are portrayed in Figure 5.
COX2↓, curcumin itself interacts with COX-2 and potentially inhibits its function
CRP↓, ole of CRP in inducing inflammation and its inhibition by curcumin are depicted in Figure 6.

2979- CUR,  GB,    Curcumin overcome primary gefitinib resistance in non-small-cell lung cancer cells through inducing autophagy-related cell death
- in-vitro, Lung, H157 - in-vitro, Lung, H1299
EGFR↓, Combination treatment with curcumin and gefitinib markedly downregulated EGFR activity through suppressing Sp1 and blocking interaction of Sp1 and HADC1,
Sp1/3/4↓,
ERK↓, and markedly suppressed receptor tyrosine kinases as well as ERK/MEK and AKT/S6K pathways in the resistant NSCLC cells.
MEK↓,
Akt↓,
S6K↓,

1443- Deg,    Deguelin Action Involves c-Met and EGFR Signaling Pathways in Triple Negative Breast Cancer Cells
- vitro+vivo, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-435 - in-vitro, BC, BT549
EGFR↓, EGFR-PAKT/c-Met p-ERK and NF-κB by down regulating their downstream targets such as p-STAT3, c-Myc, Survivin.
Akt↓, hown to inhibit AKT activation
p‑ERK↓,
NF-kB↓,
p‑STAT3↓,
survivin↓,
Myc↓,
TumCG↓,
cMET↓,

1605- EA,    Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence
- Review, Var, NA
*BioAv↓, Within the gastrointestinal tract, EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
antiOx↓, strong antioxidant properties [12,13], anti-inflammatory effects
Inflam↓,
TumCP↓, numerous studies indicate that EA possesses properties that can inhibit cell proliferation
TumCCA↑, achieved this by causing cell cycle arrest at the G1 phase
cycD1/CCND1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE/CCNE↓,
P53↑,
P21↑,
COX2↓, notable reduction in the protein expression of COX-2 and NF-κB as a result of this treatment
NF-kB↓,
Akt↑, suppressing Akt and Notch signaling pathways
NOTCH↓,
CDK2↓,
CDK6↓,
JAK↓, suppression of the JAK/STAT3 pathway
STAT3↓,
EGFR↓, decreased expression of epidermal growth factor receptor (EGFR)
p‑ERK↓, downregulated the expression of phosphorylated ERK1/2, AKT, and STAT3
p‑Akt↓,
p‑STAT3↓,
TGF-β↓, downregulation of the TGF-β/Smad3
SMAD3↓,
CDK6↓, EA demonstrated the capacity to bind to CDK6 and effectively inhibit its activity
Wnt/(β-catenin)↓, ability of EA to inhibit phosphorylation of EGFR
Myc↓, Myc, cyclin D1, and survivin, exhibited decreased levels
survivin↓,
CDK8↓, diminished CDK8 level
PKCδ↓, EA has demonstrated a notable downregulatory impact on the expression of classical isoenzymes of the PKC family (PKCα, PKCβ, and PKCγ).
tumCV↓, EA decreased cell viability
RadioS↑, further intensified when EA was combined with gamma irradiation.
eff↑, EA additionally potentiated the impact of quercetin in promoting the phosphorylation of p53 at Ser 15 and increasing p21 protein levels in the human leukemia cell line (MOLT-4)
MDM2↓, finding points to the ability of reduced MDM2 levels
XIAP↓, downregulation of X-linked inhibitor of apoptosis protein (XIAP).
p‑RB1↓, EA exerted a decrease in phosphorylation of pRB
PTEN↑, EA enhances the protein phosphatase activity of PTEN in melanoma cells (B16F10)
p‑FAK↓, reduced phosphorylation of focal adhesion kinase (FAK)
Bax:Bcl2↑, EA significantly increases the Bax/Bcl-2 rati
Bcl-xL↓, downregulates Bcl-xL and Mcl-1
Mcl-1↓,
PUMA↑, EA also increases the expression of Bcl-2 inhibitory proapoptotic proteins PUMA and Noxa in prostate cancer cells
NOXA↑,
MMP↓, addition to the reduction in MMP, the release of cytochrome c into the cytosol occurs in pancreatic cancer cells
Cyt‑c↑,
ROS↑, induction of ROS production
Ca+2↝, changes in intracellular calcium concentration, leading to increased levels of EndoG, Smac/DIABLO, AIF, cytochrome c, and APAF1 in the cytosol
Endoglin↑,
Diablo↑,
AIF↑,
iNOS↓, decreased expression of Bcl-2, NF-кB, and iNOS were observed after exposure to EA at concentrations of 15 and 30 µg/mL
Casp9↑, increase in caspase 9 activity in EA-treated pancreatic cancer cells PANC-1
Casp3↑, EA-induced caspase 3 activation and PARP cleavage in a dose-dependent manner (10–100 µmol/L)
cl‑PARP↑,
RadioS↑, EA sensitizes and reduces the resistance of breast cancer MCF-7 cells to apoptosis induced by γ-radiation
Hif1a↓, EA reduced the expression of HIF-1α
HO-1↓, EA significantly reduced the levels of two isoforms of this enzyme, HO-1, and HO-2, and increased the levels of sEH (Soluble epoxide hydrolase) in LnCap
HO-2↓,
SIRT1↓, EA-induced apoptosis was associated with reduced expression of HuR and Sirt1
selectivity↑, A significant advantage of EA as a potential chemopreventive, anti-tumor, or adjuvant therapeutic agent in cancer treatment is its relative selectivity
Dose∅, EA significantly reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
NHE1↓, EA had the capacity to regulate cytosolic pH by downregulating the expression of the Na+/H+ exchanger (NHE1)
Glycolysis↓, led to intracellular acidification with subsequent impairment of glycolysis
GlucoseCon↓, associated with a decrease in the cellular uptake of glucose
lactateProd↓, notable reduction in lactate levels in supernatant
PDK1?, inhibit pyruvate dehydrogenase kinase (PDK) -bind and inhibit PDK3
PDK1?,
ECAR↝, EA has been shown to influence extracellular acidosis
COX1↓, downregulation of cancer-related genes, including COX1, COX2, snail, twist1, and c-Myc.
Snail↓,
Twist↓,
cMyc↓,
Telomerase↓, EA, might dose-dependently inhibit telomerase activity
angioG↓, EA may inhibit angiogenesis
MMP2↓, EA demonstrated a notable reduction in the secretion of matrix metalloproteinase (MMP)-2 and MMP-9.
MMP9↓,
VEGF↓, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
Dose↝, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
PD-L1↓, EA downregulated the expression of the immune checkpoint PD-L1 in tumor cells
eff↑, EA might potentially enhance the efficacy of anti-PD-L1 treatment
SIRT6↑, EA exhibited statistically significant upregulation of sirtuin 6 at the protein level in Caco2 cells
DNAdam↓, increase in DNA damage

26- EGCG,  QC,  docx,    Green tea and quercetin sensitize PC-3 xenograft prostate tumors to docetaxel chemotherapy
- vitro+vivo, Pca, PC3
BAD↓,
cl‑PARP↑,
Casp7↑,
IκB↓,
Ki-67↓,
VEGF↓,
EGFR↓,
FGF↓,
TGF-β↓,
TNF-α↓,
SCF↓,
Bax:Bcl2↑,
NF-kB↓,
chemoP↑, This study provides a novel regimen to enhance the therapeutic effect of Doc in a less-toxic manner and reduce its risk of side effects in treatment of CRPC.
ChemoSen↑, GT and Q with LD Doc significantly enhanced the potency of Doc 2-fold and reduced tumor growth by 62 % compared to LD Doc in 7-weeks intervention.
TumVol↓,

20- EGCG,    Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer
- in-vivo, Liver, NA - in-vivo, Tong, NA
HH↓,
Gli1↓,
Smo↓,
TNF-α↓,
COX2↓, EGCG inhibits cyclooxygenase-2 without affecting COX-1 expression at both the mRNA and protein levels, in androgen-sensitive LNCaP and androgen-insensitive PC-3
*antiOx↑, EGCG is a well-known antioxidant and it scavenges most free radicals, such as ROS and RNS
Hif1a↓,
NF-kB↓,
VEGF↓,
STAT3↓,
Bcl-2↓,
P53↑, EGCG activates p53 in human prostate cancer cells
Akt↓,
p‑Akt↓,
p‑mTOR↓,
EGFR↓,
AP-1↓,
BAX↑,
ROS↑, apoptosis was convoyed by ROS production and caspase-3 cleavage
Casp3↑,
Apoptosis↑,
NRF2↑, pancreatic cancer cells via inducing cellular reactive oxygen species (ROS) accumulation and activating Nrf2 signaling
*H2O2↓, EGCG plays a role in the inhibition of H2O2 and NO production in human skin [10].
*NO↓, EGCG plays a role in the inhibition of H2O2 and NO production in human skin [10].
*SOD↑, fig 2
*Catalase↑, fig 2
*GPx↑, fig 2
*ROS↓, fig 2

643- EGCG,    New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate
- Analysis, NA, NA
H2O2↑,
Fenton↑,
PDGFR-BB↑,
EGFR↓, EGCG inhibits activities of EGFR, VEGFR, and IGFR
VEGFR2↓,
IGFR↓,
Ca+2↑, EGCG elevates cytosolic Ca2+ levels
NO↑, EGCG-stimulated elevation of cytosolic calcium contributes to NO production by binding to calmodulin
Sp1/3/4↓,
NF-kB↓,
AP-1↓,
STAT1↓,
STAT3↓,
FOXO↓, FOXO1
mtDam↑,
TumAuto↑,


Showing Research Papers: 1 to 50 of 122
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 122

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   Fenton↑, 1,   Ferroptosis↑, 2,   GPx4↓, 1,   H2O2↑, 1,   HO-1↓, 2,   HO-2↓, 1,   lipid-P↑, 1,   NRF2↓, 6,   NRF2↑, 3,   ROS↓, 1,   ROS↑, 18,   SOD2↓, 1,   xCT↓, 1,  

Metal & Cofactor Biology ⓘ

TfR1/CD71↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   ATP↓, 1,   BCR-ABL↓, 1,   CDC2↓, 1,   EGF↑, 1,   MEK↓, 3,   MMP↓, 6,   MMP↑, 1,   Mortalin↓, 1,   mtDam↑, 1,   Raf↓, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AKT1↓, 1,   ALAT↓, 1,   AMPK↑, 6,   AMPK↝, 1,   cMyc↓, 5,   ECAR↝, 1,   FASN↓, 1,   FDG↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 3,   HK2↓, 1,   IR↓, 1,   lactateProd↓, 1,   LDH↓, 1,   LDL↓, 1,   PDH↑, 2,   PDK1?, 2,   PDK1↓, 1,   PI3K/Akt↓, 1,   PI3k/Akt/mTOR↓, 1,   PIK3CA↓, 1,   PPARα↓, 1,   PPARγ↑, 1,   S6K↓, 1,   p‑S6K↓, 1,   SIRT1↓, 2,   SREBP1↓, 1,  

Cell Death ⓘ

Akt↓, 17,   Akt↑, 1,   p‑Akt↓, 6,   APAF1↑, 1,   Apoptosis↑, 17,   BAD↓, 1,   BAD↑, 1,   BAX↑, 7,   BAX↝, 1,   Bax:Bcl2↑, 5,   Bcl-2↓, 6,   Bcl-2↑, 1,   Bcl-2↝, 1,   Bcl-xL↓, 3,   BID↑, 1,   Casp↑, 2,   Casp1↑, 1,   Casp3↑, 11,   Casp3↝, 1,   cl‑Casp3↑, 1,   proCasp3↓, 1,   Casp7↑, 1,   cl‑Casp7↑, 1,   Casp8↑, 4,   cl‑Casp8↑, 1,   Casp9↑, 8,   cl‑Casp9↑, 1,   p‑Chk2↑, 1,   CK2↓, 3,   Cyt‑c↑, 8,   Cyt‑c↝, 1,   Diablo↑, 2,   DR5↑, 1,   Fas↑, 2,   FasL↑, 1,   Ferroptosis↑, 2,   hTERT/TERT↓, 1,   cl‑IAP2↑, 1,   iNOS↓, 2,   JNK↓, 1,   JNK↑, 2,   p‑JNK↓, 2,   MAPK↓, 3,   Mcl-1↓, 3,   MDM2↓, 1,   Myc↓, 2,   NOXA↑, 1,   oncosis↑, 1,   p27↑, 3,   p‑p38↑, 1,   PUMA↑, 1,   survivin↓, 4,   Telomerase↓, 5,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 4,   PAK↓, 1,   RTK-RAS↓, 1,   Sp1/3/4↓, 5,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   miR-21↓, 1,   other↝, 3,   p‑pRB↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

p‑eIF2α↑, 1,   ER Stress↑, 1,   GRP78/BiP↓, 1,   GRP78/BiP↑, 1,   HSP70/HSPA5↓, 1,   HSP90↓, 2,   HSPs↓, 1,   UPR↑, 1,   XBP-1↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   TumAuto↑, 4,  

DNA Damage & Repair ⓘ

p‑ATM↑, 1,   p‑ATR↑, 1,   p‑CHK1↑, 1,   DNAdam↓, 1,   DNAdam↑, 6,   DNMT1↓, 2,   m-FAM72A↓, 1,   HR↓, 1,   p16↑, 1,   P53↓, 2,   P53↑, 7,   PARP↑, 2,   PARP↝, 1,   cl‑PARP↑, 4,   cl‑PARP1↑, 1,   RAD51↓, 1,   SIRT6↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 2,   CDK2↓, 2,   CDK4↓, 5,   cycD1/CCND1↓, 7,   cycD1/CCND1↝, 1,   cycE/CCNE↓, 3,   cycE1↓, 1,   P21↑, 5,   P21↝, 1,   p‑RB1↓, 1,   TumCCA?, 1,   TumCCA↓, 1,   TumCCA↑, 16,  

Proliferation, Differentiation & Cell State ⓘ

ALDH1A1↓, 1,   CD133↓, 3,   CD44↓, 2,   CDK8↓, 1,   cMET↓, 2,   cMYB↓, 1,   CSCs↓, 5,   Diff↓, 1,   EIF4E↓, 1,   EMT↓, 5,   ERK↓, 10,   p‑ERK↓, 2,   p‑ERK⇅, 1,   FGF↓, 2,   FOXO↓, 1,   Gli1↓, 3,   GSK‐3β↓, 2,   p‑GSK‐3β↓, 1,   HDAC↓, 1,   HH↓, 1,   IGF-1↓, 1,   IGFBP3↑, 1,   IGFR↓, 2,   mTOR↓, 12,   mTOR↝, 1,   p‑mTOR↓, 2,   p‑mTORC1↓, 1,   n-MYC↓, 1,   Nanog↓, 1,   Nestin↓, 1,   NOTCH↓, 4,   NOTCH1↓, 2,   NOTCH1↑, 1,   NOTCH3↓, 1,   OCT4↓, 1,   P70S6K↓, 1,   PI3K↓, 11,   PRKCG↑, 1,   PTCH1↓, 1,   PTEN↑, 2,   RPS6KA1↓, 1,   SCF↓, 1,   Shh↓, 1,   Smo↓, 2,   SOX2↓, 2,   Src↓, 1,   STAT1↓, 2,   STAT3↓, 11,   p‑STAT3↓, 4,   STAT4↓, 1,   STAT5↓, 1,   TOP1↓, 3,   TOP2↓, 2,   TRPM7↓, 1,   TumCG↓, 8,   Wnt↓, 4,   Wnt/(β-catenin)↓, 3,  

Migration ⓘ

annexin II↓, 1,   AntiAg↑, 1,   AP-1↓, 3,   ATPase↓, 2,   Ca+2↑, 3,   Ca+2↝, 1,   cal2↑, 1,   CD31↓, 1,   CDK4/6↓, 1,   CLDN1↓, 1,   E-cadherin↓, 2,   E-cadherin↑, 2,   FAK↓, 1,   p‑FAK↓, 1,   Fibronectin↓, 1,   GLI2↓, 1,   ITGB1↑, 1,   ITGB4↓, 1,   Ki-67↓, 2,   KRAS↓, 1,   miR-133a-3p↑, 1,   MMP-10↓, 1,   MMP17↓, 1,   MMP2↓, 7,   MMP9↓, 7,   MMPs↓, 5,   NCAM↑, 1,   p44↓, 1,   PDGF↓, 1,   PKCδ↓, 1,   ROCK1↓, 2,   Slug↓, 1,   SMAD3↓, 1,   Snail↓, 2,   TET1↑, 1,   TGF-β↓, 4,   TGF-β1↓, 1,   TIMP2↑, 1,   TumCI↓, 9,   TumCMig↓, 4,   TumCP↓, 10,   TumMeta↓, 8,   Twist↓, 2,   uPA↓, 1,   Vim↓, 3,   β-catenin/ZEB1↓, 7,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   ECM/TCF↓, 1,   EGFR↓, 49,   p‑EGFR↓, 1,   EGR4↓, 1,   Endoglin↑, 1,   Hif1a↓, 12,   KDR/FLK-1↓, 1,   NO↓, 1,   NO↑, 1,   PDGFR-BB↑, 1,   VEGF↓, 17,   VEGFR2↓, 2,   p‑VEGFR2↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   NHE1↓, 1,   P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

CCR7↓, 1,   COX1↓, 1,   COX2↓, 9,   COX2↑, 2,   COX2↝, 1,   CRP↓, 1,   CXCR4↓, 1,   IL1↓, 2,   IL10↓, 1,   IL12↓, 1,   IL18↓, 1,   IL1β↓, 1,   IL2↓, 1,   IL5↓, 1,   IL6↓, 4,   IL8↓, 2,   Imm↑, 1,   Inflam↓, 2,   IκB↓, 1,   JAK↓, 2,   JAK1↓, 1,   JAK2↓, 2,   p‑JAK2↓, 1,   MCP1↓, 1,   MIP2↓, 1,   NF-kB↓, 18,   p65↓, 1,   PD-1↝, 1,   PD-L1↓, 1,   PGE2↓, 5,   PSA↓, 1,   TLR4↓, 1,   TNF-α↓, 4,  

Hormonal & Nuclear Receptors ⓘ

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

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 3,   BioAv↝, 2,   ChemoSen↑, 16,   Dose?, 1,   Dose↓, 1,   Dose↑, 1,   Dose↝, 3,   Dose∅, 1,   eff↑, 22,   eff↝, 4,   Half-Life↓, 1,   Half-Life↑, 2,   RadioS↑, 6,   selectivity↑, 4,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AR↓, 2,   CRP↓, 1,   EGFR↓, 49,   p‑EGFR↓, 1,   GutMicro↑, 1,   HER2/EBBR2↓, 4,   hTERT/TERT↓, 1,   IL6↓, 4,   Ki-67↓, 2,   KRAS↓, 1,   LDH↓, 1,   Myc↓, 2,   PD-L1↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 4,   AntiTum↑, 2,   cardioP↑, 1,   chemoP↑, 2,   chemoPv↑, 2,   neuroP↑, 1,   OS↑, 4,   QoL↑, 4,   RenoP↑, 1,   toxicity↝, 1,   TumVol↓, 1,  
Total Targets: 355

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx?, 1,   antiOx↑, 5,   Catalase↑, 1,   GPx↑, 2,   GSH↑, 1,   H2O2↓, 1,   lipid-P↓, 2,   NRF2↑, 1,   ROS↓, 4,   SOD↑, 2,  

Metal & Cofactor Biology ⓘ

IronCh↑, 2,  

Core Metabolism/Glycolysis ⓘ

GlucoseCon↑, 1,  

Cell Death ⓘ

iNOS↓, 1,   MAPK↓, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 1,   other↓, 1,   other↝, 1,  

Migration ⓘ

PKCδ↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 9,   NF-kB↓, 2,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   ChAT↑, 1,  

Protein Aggregation ⓘ

BACE↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CYP19↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 7,   BioAv↑, 3,   BioAv↝, 3,   eff↑, 1,   Half-Life↓, 3,  

Clinical Biomarkers ⓘ

ALP↓, 1,   AST↓, 2,   GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiAge↑, 1,   AntiDiabetic↑, 1,   cardioP↓, 1,   cardioP↑, 3,   cognitive↑, 1,   hepatoP↑, 2,   memory↑, 3,   motorD↑, 1,   neuroP↑, 6,   Obesity↓, 1,   toxicity↓, 2,   Wound Healing↑, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 2,  
Total Targets: 50

Scientific Paper Hit Count for: EGFR, Epidermal Growth Factor Receptor
11 Fisetin
10 Quercetin
9 EGCG (Epigallocatechin Gallate)
8 Curcumin
8 Honokiol
6 Shikonin
5 Silymarin (Milk Thistle) silibinin
4 almonertinib
4 Berberine
3 Artemisinin
3 Bufalin/Huachansu
3 brusatol
3 Resveratrol
3 Sulforaphane (mainly Broccoli)
2 Alpha-Lipoic-Acid
2 Apigenin (mainly Parsley)
2 Betulinic acid
2 Brucea javanica
2 cetuximab
2 Docetaxel
2 Gallic acid
2 Graviola
2 Luteolin
2 Piperlongumine
1 Astragalus
1 Silver-NanoParticles
1 Allicin (mainly Garlic)
1 Ashwagandha(Withaferin A)
1 Astaxanthin
1 Aloe anthraquinones
1 Biochanin A
1 Chemotherapy
1 Boron
1 Capsaicin
1 Caffeic Acid Phenethyl Ester (CAPE)
1 Carvacrol
1 Thymol-Thymus vulgaris
1 Chlorogenic acid
1 Chrysin
1 Photodynamic Therapy
1 gefitinib, erlotinib
1 Deguelin
1 Ellagic acid
1 Piperine
1 Gambogic Acid
1 Licorice
1 Lycopene
1 Magnetic Fields
1 Myricetin
1 Naringin
1 Niclosamide (Niclocide)
1 Phenethyl isothiocyanate
1 Gold NanoParticles
1 Rosmarinic acid
1 Gemcitabine (Gemzar)
1 statins
1 Citric Acid
1 Thymoquinone
1 Ursolic acid
1 β‐Elemene
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#:94  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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