PI3K Cancer Research Results

PI3K, Phosphatidylinositide-3-Kinases: Click to Expand ⟱
Source: HalifaxProj(inhibit) CGL-CS
Type:
Phosphatidylinositol 3-kinase (PtdIns3K or PI3K) is a family of enzymes that play a crucial role in cell signaling pathways, particularly in the regulation of cell growth, survival, and metabolism. The PI3K pathway is one of the most frequently altered pathways in human cancer. Inhibition of the PI3K pathway has been explored as a therapeutic strategy for cancer treatment. Several PI3K inhibitors have been developed and are currently being tested in clinical trials. These inhibitors can target specific components of the pathway, such as PI3K, AKT, or mTOR.

Class I phosphoinositide 3-kinase (PI3K)
Class III PtdIns3K
In contrast to the class III PtdIns3K as a positive regulator of autophagy, class I PI3K-AKT signaling has an opposing effect on the initiation of autophagy.

PI3K inhibitors include:
-Idelalisib , Copanlisib, Alpelisib
-LY294002?
-Wortmannin: potent PI3K inhibitor, has some associated toxicity.
-Quercetin:
-Curcumin
-Resveratrol
-Epigallocatechin Gallate (EGCG)
Scientific Papers found: Click to Expand⟱
4774- 5-FU,  TQ,  CoQ10,    Exploring potential additive effects of 5-fluorouracil, thymoquinone, and coenzyme Q10 triple therapy on colon cancer cells in relation to glycolysis and redox status modulation
- in-vitro, CRC, NA
AntiCan↑, All treatments resulted in anticancer effects depicted by cell cycle arrest and apoptosis, with TQ demonstrating greater efficacy than CQ10, both with and without 5-FU.
TumCCA↑,
Apoptosis↑,
eff↑,
Bcl-2↓, However, 5-FU/TQ/CQ10 triple therapy exhibited the most potent pro-apoptotic activity in all cell lines, portrayed by the lowest levels of oncogenes (CCND1, CCND3, BCL2, and survivin)
survivin↓,
P21↑, and the highest upregulation of tumour suppressors (p21, p27, BAX, Cytochrome-C, and Cas- pase-3).
p27↑,
BAX↑,
Cyt‑c↑,
Casp3↑,
PI3K↓, The triple therapy also showed the strongest suppression of the PI3K/AKT/mTOR/HIF1α pathway, with a concurrent increase in its endogenous inhibitors (PTEN and AMPKα) in all cell lines used.
Akt↓,
mTOR↓,
Hif1a↓,
PTEN↑,
AMPKα↑,
PDH↑, triple therapy favoured glucose oxidation by upregulating PDH, while decreasing LDHA and PDHK1 enzymes.
LDHA↓,
antiOx↓, most significant decline in antioxidant levels and the highest increases in oxidative stress markers
ROS↑,
AntiCan↑, This study is the first to demonstrate the superior anticancer effects of TQ compared to CQ10, with and without 5-FU, in CRC treatment.

5468- AF,    The gold complex auranofin: new perspectives for cancer therapy
- Review, Var, NA
TrxR↓, Auranofin mainly targets the anti-oxidative system catalyzed by thioredoxin reductase (TrxR), which protects the cell from oxidative stress and death in the cytoplasm and the mitochondria.
ROS↑, Inhibiting TrxR dysregulates the intracellular redox state causing increased intracellular reactive oxygen species levels, and stimulates cellular demise
eff↑, TrxR is over-expressed in many cancers as an adaptive mechanism for cancer cell proliferation, rendering it an attractive target for cancer therapy, and auranofin as a potential therapeutic agent for cancer.
Apoptosis↑, promotion of ASK-induced apoptosis, and blockage of cell growth, proliferation, and survival due to reduced AKT activity and NF-kB- and p53-mediated transcription.
TumCG↓,
TumCP↓,
Akt↓,
NF-kB↓,
DNAdam↑, DNA damage
eff↝, auranofin inhibits TrxR1 in a p53-independent manner
eff↓, Pre-treatment with NAC counteracted the cancer cell killing effects of auranofin,
PI3K↓, auranofin induces cytotoxicity in human pancreatic adenocarcinoma and non-small cell lung cancer via the inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Hif1a↓, auranofin inhibits the cancer cell response to hypoxia, demonstrated by a decrease in HIF-1 𝛼 expression and VEGF secretion upon auranofin treatment under hypoxic conditions
VEGF↓,
Casp3↑, auranofin was shown to induce caspase-3-mediated apoptosis in human ovarian carcinoma SKOV-3 cells
CSCs↓,
ATP↓, it was found that auranofin inhibits ABCG2 function by depleting cellular ATP via inhibition of glycolysis [96]
Glycolysis↓,
eff↑, auranofin synergizes with another Trx1 inhibitor, piperlongumine, in killing gastric cancer cells in association with ROS-mediated ER stress response and mitochondrial dysfunction.
eff↑, when the gold complex is combined with either selenite or tellurite [104]
MMP↓, Increased ROS induced by AUR causes decreased membrane potential in the mitochondrial membrane, resulting in a decrease in anti-apoptotic proteins, caspase-dependent cell death, and translocation of apoptosis-inducing factor (AIF)
AIF↑,
toxicity↓, Auranofin is considered safe for human use in treating rheumatoid arthritis; thus, this gold derivative can reach the clinic for other diseases relatively quickly and at a low cost

1335- AG,    Extract from Astragalus membranaceus inhibit breast cancer cells proliferation via PI3K/AKT/mTOR signaling pathway
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, SkBr3
p‑PI3K↓,
p‑GS3Kβ↓,
p‑Akt↓,
p‑mTOR↓,

5444- AG,    A Systematic Review of Phytochemistry, Pharmacology and Pharmacokinetics on Astragali Radix: Implications for Astragali Radix as a Personalized Medicine
- Review, Var, NA
*Imm↑, AR possesses various biological functions, including potent immunomodulation, antioxidant, anti-inflammation and antitumor activities.
*antiOx↑,
*Inflam↓,
AntiTum↑,
eff↑, characteristics of increasing curative effect and reducing the toxicity of chemotherapeutic drugs [11 , 118].
chemoP↑,
Dose↝, main bioactive compounds responsible for the anti-cancer effects of AR mainly include formononetin, AS-IV and APS. S
TumCMig↓, AS-IV could inhibit the migration and proliferation of non-small cell lung cancer (NSCLC
TumCP↓,
Akt↓, h via inhibition of the Akt/GSK-3β/β-catenin signaling axis.
GSK‐3β↓,
MMP2↓, downregulating the expression of matrix metalloproteases (MMP)-2 and -9
MMP9↓,
EMT↓, AS-IV could inhibit TGF-B1 induced EMT through inhibition of PI3K/AKT/NF-KB
PI3K↓,
Akt↓,
NF-kB↓,
Inflam↓,
TGF-β1↓,
TNF-α↓,
IL6↓,
Fas↓, reduced FAS/FasL
FasL↓,
NOTCH1↓, decressing notch1
JNK↓, inactivating JNK pathway [145]
TumCG↓, The results showed that the AR water extract could inhibit the growth of colorectal cancer in vivo without apparent toxicity and side effect, which suggests that AR is a potential therapeutic drug for colorectal cancer

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

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

4426- AgNPs,    Antiangiogenic properties of silver nanoparticles
- Study, NA, NA
angioG↑, Ag-NPs might have the ability to inhibit angiogenesis, the pivotal step in tumor growth, invasiveness, and metastasis.
TumCG↓,
TumCI↓,
TumMeta↓,
VEGF↓, demonstrated that Ag-NPs could also inhibit vascular endothelial growth factor (VEGF) induced cell proliferation, migration, and capillary-like tube formation of bovine retinal endothelial cells like PEDF.
PI3K↓, inhibition of the PI3K/Akt cell-survival signal in a similar pattern of PEDF.
Akt↓,

4549- AgNPs,    Silver nanoparticles: Synthesis, medical applications and biosafety
- Review, Var, NA - Review, Diabetic, NA
ROS↑, action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS), destruction of membrane structure.
eff↑, briefly introduce a new type of Ag particles smaller than AgNPs, silver Ångstrom (Å, 1 Å = 0.1 nm) particles (AgÅPs), which exhibit better biological activity and lower toxicity compared with AgNPs.
other↝, This method involves reducing silver ions to silver atoms 9, and the process can be divided into two steps, nucleation and growth
DNAdam↑, antimicrobial mechanisms of AgNPs includes destructing bacterial cell walls, producing reactive oxygen species (ROS) and damaging DNA structure
EPR↑, Due to the enhanced permeability and retention (EPR) effect, tumor cells preferentially absorb NPs-sized bodies than normal tissues
eff↑, Large surface area may lead to increased silver ions (Ag+) released from AgNPs, which may enhance the toxicity of nanoparticles.
eff↑, Our team prepared Ångstrom silver particles, capped with fructose as stabilizer, can be stable for a long time
TumMeta↓, AgNPs can induce tumor cell apoptosis through inactivating proteins and regulating signaling pathways, or blocking tumor cell metastasis by inhibiting angiogenesis
angioG↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
*Bacteria↓, Rather than Gram-positive bacteria, AgNPs show a stronger effect on the Gram-negative ones. This may be due to the different thickness of cell wall between two kinds of bacteria
*eff↑, In general, as particle size decreases, the antibacterial effect of AgNPs increases significantly
*AntiViral↑, AgNPs with less than 10 nm size exhibit good antiviral activity 185, 186, which may be due to their large reaction area and strong adhesion to the virus surface.
*AntiFungal↑, Some studies confirm that AgNPs exhibit good antifungal properties against Colletotrichum coccodes, Monilinia sp. 178, Candida spp.
eff↑, The greater cytotoxicity and more ROS production are observed in tumor cells exposed to high positive charged AgNPs
eff↑, Nanoparticles exposed to a protein-containing medium are covered with a layer of mixed protein called protein corona. formation of protein coronas around AgNPs can be a prerequisite for their cytotoxicity
TumCP↓, Numerous experiments in vitro and in vivo have proved that AgNPs can decrease the proliferation and viability of cancer cells.
tumCV↓,
P53↝, gNPs can promote apoptosis by up- or down-regulating expression of key genes, such as p53 242, and regulating essential signaling pathways, such as hypoxia-inducible factor (HIF) pathway
HIF-1↓, Yang et al. found that AgNPs could disrupt the HIF signaling pathway by attenuating HIF-1 protein accumulation and downstream target genes expression
TumCCA↑, Cancer cells treated with AgNPs may also show cell cycle arrest 160, 244
lipid-P↑, Ag+ released by AgNPs induces oxidation of glutathione, and increases lipid peroxidation in cellular membranes, resulting in cytoplasmic constituents leaking from damaged cells
ATP↓, mitochondrial function can be inhibited by AgNPs via disrupting mitochondrial respiratory chain, suppressing ATP production
Cyt‑c↑, and the release of Cyt c, destroy the electron transport chain, and impair mitochondrial function
MMPs↓, AgNPs can also inhibit the progression of tumors by inhibiting MMPs activity.
PI3K↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
Akt↓,
*Wound Healing↑, AgNPs exhibit good properties in promoting wound repair and bone healing, as well as inhibition of inflammation.
*Inflam↓,
*Bone Healing↑,
*glucose↓, blood glucose level of diabetic rats decreased when treated with AgNPs for 14 days and 21 days without significant acute toxicity.
*AntiDiabetic↑,
*BBB↑, The small-sized AgNPs are easy to penetrate the body and cross biological barriers like the blood-brain barrier and the blood-testis barrier

377- AgNPs,    Anticancer Action of Silver Nanoparticles in SKBR3 Breast Cancer Cells through Promotion of Oxidative Stress and Apoptosis
- in-vitro, BC, SkBr3
ROS↑,
Apoptosis↑,
Bax:Bcl2↑,
VEGF↑, VEGF-A
Akt↓,
PI3K↓,
TAC↓,
TOS↑,
OSI↑,
MDA↑,
Casp3↑,
Casp7↑,

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

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

250- AL,    Allicin Induces p53-Mediated Autophagy in Hep G2 Human Liver Cancer Cells
- in-vitro, Liver, HepG2
P53↓, allicin decreased the level of cytoplasmic p53, the PI3K/mTOR signaling pathway
PI3K↓, decreased the levels of PI3K/mTOR, p-Bcl-2, Bcl-xL, and cytoplasmic p53 in Hep G2 cells.
mTOR↓,
Bcl-2↓,
AMPK↑,
TSC2↑,
Beclin-1↑, llicin increased the levels of Beclin-1, Bad, p-AMPK, TSC2, and Atg7
TumAuto↑, Allicin induced autophagy and increased the formation of autophagosomes and autophagolysosomes in Hep G2 cells.
tumCV↓, Allicin treatment at 35 uM decreased the viability of Hep G2 cells after 12 and 24 h significantly.
ATG7↑,
MMP↓, allicin treatment caused a decrease of MMP of Hep G2 cells and degradation of mitochondria

3272- ALA,    Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
- Review, AD, NA
*antiOx↑, LA has long been touted as an antioxidant,
*glucose↑, improve glucose and ascorbate handling,
*eNOS↑, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*NRF2↑,
*MMP9↓,
*VCAM-1↓,
*NF-kB↓,
*cardioP↑, used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits,
*cognitive↑,
*eff↓, The efficiency of LA uptake was also lowered by its administration in food,
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies;
*IronCh↑, LA preferentially binds to Cu2+, Zn2+ and Pb2+, but cannot chelate Fe3+, while DHLA forms complexes with Cu2+, Zn2+, Pb2+, Hg2+ and Fe3+
*GSH↑, LA markedly increases intracellular glutathione (GSH),
*PKCδ↑, PKCδ, LA activates Erk1/2 [92,93], p38 MAPK [94], PI3 kinase [94], and Akt
*ERK↑,
*p38↑,
*MAPK↑,
*PI3K↑,
*Akt↑,
*PTEN↓, LA decreases the activities of Protein Tyrosine Phosphatase 1B [99], Protein Phosphatase 2A [95], and the phosphatase and tensin homolog PTEN [95],
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, stimulate GLUT4 translocation
*GLUT1↑, LA-stimulated translocation of GLUT1 and GLUT4.
*Inflam↓, LA as an anti-inflammatory agent

3434- ALA,    Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
tumCV↓, significant dose-dependent reduction in cell viability, with the half-maximal inhibitory concentration (IC50) of LA to be 3.2 mM for MCF-7 cells and 2.9 mM for MDA-MB-231 cells
PI3K↓, LA significantly inhibited PI3K, p-AKT, p-p70S6K and p-mTOR levels
p‑Akt↓,
p‑P70S6K↓,
mTOR↓,
ATP↓, LA markedly reduced both ATP levels and glucose uptake (Fig. 4A and 4B). LA also induced ROS generation in both MCF-7 and MDA-MB231 spheroids
GlucoseCon↓,
ROS↑,
PKM2↓, LA downregulated the expression of PKM2 and LDHA in the spheroids, indicating an inhibition of glycolysis in BCSCs
LDHA↓,
Glycolysis↓,
ChemoSen↑, LA enhances chemosensitivity of spheroids to Dox treatment

3436- ALA,    Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights Author links open overlay panel
- in-vitro, BC, MCF-7
ChemoSen↑, LA also enhanced the sensitivity of breast cancer spheroids to doxorubicin (Dox), demonstrating a synergistic effect.
PI3K↓, LA inhibits PI3K/AKT signaling in breast cancer spheroids
Akt↓,
ATP↓, found that LA markedly reduced both ATP levels and glucose uptake
GlucoseCon↓,
ROS↑, LA also induced ROS generation in both MCF-7 and MDA-MB231 spheroids
PKM2↓, LA downregulated the expression of PKM2 and LDHA in the spheroids, indicating an inhibition of glycolysis in BCSCs
Glycolysis↓,
CSCs↓,
IGF-1R↓, LA inhibits IGF-1R via furin downregulation, synergizes with other anticancer drugs like paclitaxel and cisplatin, and enhances radiosensitivity in breast cancer
Furin↓,
RadioS↑,

3437- ALA,    Revisiting the molecular mechanisms of Alpha Lipoic Acid (ALA) actions on metabolism
- Review, Var, NA
*IronCh↑, ALA functions as a metabolic regulator, metal chelator, and a powerful antioxidant.
*antiOx↑,
*ROS↓, It quenches reactive oxygen species (ROS), restores exogenous and endogenous antioxidants such as vitamins and Glutathione (GSH), and repairs oxidized proteins
*GSH↑,
*NF-kB↓, inhibition of the activation of nuclear factor kappa B (NF-κB)
*AMPK⇅, activation of peripheral AMPK and inhibition of hypothalamic AMPK
*FAO↑, ALA has been found to activate peripheral AMPK, thereby enhancing fatty acid oxidation and glucose uptake in muscle cells
*GlucoseCon↑,
*PI3K↑, It stimulates glucose uptake by increasing the activity of PI3K and Akt which are crucial for the translocation of glucose transporters like GLUT4 to the cell membrane, mimicking the action of insulin
*Akt?,

3539- ALA,    Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
- Review, AD, NA
*ROS↓, scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age.
*IronCh↑, LA preferentially binds to Cu2+, Zn2+ and Pb2+, but cannot chelate Fe3+, while DHLA forms complexes with Cu2+, Zn2+, Pb2+, Hg2+ and Fe3+
*GSH↑,
*antiOx↑, LA has long been touted as an antioxidant
*NRF2↑, activate Phase II detoxification via the transcription factor Nrf2
*MMP9↓, lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*VCAM-1↓,
*NF-kB↓,
*cognitive↑, it has been used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits, and has been implicated as a modulator of various inflammatory signaling pathways
*Inflam↓,
*BioAv↝, LA bioavailability may be dependent on multiple carrier proteins.
*BioAv↝, observed that approximately 20-40% was absorbed [
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies
*H2O2∅, Neither species is active against hydrogen peroxide
*neuroP↑, chelation of iron and copper in the brain had a positive effect in the pathobiology of Alzheimer’s Disease by lowering free radical damage
*PKCδ↑, In addition to PKCδ, LA activates Erk1/2 [92, 93], p38 MAPK [94], PI3 kinase [94], and Akt [94-97].
*ERK↑,
*MAPK↑,
*PI3K↑,
*Akt↑,
*PTEN↓, LA decreases the activities of Protein Tyrosine Phosphatase 1B [99], Protein Phosphatase 2A [95], and the phosphatase and tensin homolog PTEN
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, In skeletal muscle, LA is proposed to recruit GLUT4 from its storage site in the Golgi to the sarcolemma, so that glucose uptake is stimulated by the local increase in transporter abundance.
*GlucoseCon↑,
*BP↝, Feeding LA to hypertensive rats normalized systolic blood pressure and cytosolic free Ca2+
*eff↑, Clinically, LA administration (in combination with acetyl-L-carnitine) showed some promise as an antihypertensive therapy by decreasing systolic pressure in high blood pressure patients and subjects with the metabolic syndrome
*ICAM-1↓, decreased demyelination and spinal cord expression of adhesion molecules (ICAM-1 and VCAM-1)
*VCAM-1↓,
*Dose↝, Considering the transient cellular accumulation of LA following an oral dose, which does not exceed low micromolar levels, it is entirely possible that some of the cellular effects of LA when given at supraphysiological concentrations may be not be c

285- ALA,  HCA,    Tolerance of oral lipoid acid and hydroxycitrate combination in cancer patients: first approach of the cancer metabolism research group
- Human, Var, NA
PI3K↝,
AMPK↝,
TumCG↓,
*toxicity↓, No hepatic toxicity found, no weight loss, no hypoglycemia
Weight∅,

4283- ALC,    Rapid-acting antidepressant-like effects of acetyl-l-carnitine mediated by PI3K/AKT/BDNF/VGF signaling pathway in mice
- in-vivo, NA, NA
*BDNF↑, In addition, ALC (100 mg/kg, i.p.) also reversed depressive-like behavior and the down-regulation of phosphorylated AKT (pAKT), brain-derived neurotrophic factor (BDNF) and neuropeptide VGF in the hippocampus and prefrontal cortex of mice induced by
*p‑Akt↑,
*PI3K↑,

1279- And,    Andrographolide Exhibits Anticancer Activity against Breast Cancer Cells (MCF-7 and MDA-MB-231 Cells) through Suppressing Cell Proliferation and Inducing Cell Apoptosis via Inactivation of ER-α Receptor and PI3K/AKT/mTOR Signaling
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7
Apoptosis↑,
Bcl-2↓,
BAX↑,
ERα/ESR1↓, ER-positive
PI3K↓, ER-positive
mTOR↓, ER-positive BC

4280- Api,    Protective effects of apigenin in neurodegeneration: An update on the potential mechanisms
- Review, AD, NA - Review, Park, NA
*neuroP↑, Apigenin, a flavonoid found in various herbs and plants, has garnered significant attention for its neuroprotective properties
*antiOx↑, shown to possess potent antioxidant activity, which is thought to play a crucial role in its neuroprotective effects
*ROS↓, Apigenin has been demonstrated to scavenge ROS, thereby reducing oxidative stress and mitigating the damage to neurons
*Inflam↓, apigenin has been found to possess anti-inflammatory properties.
*TNF-α↓, inhibit the production of pro-inflammatory cytokines, such as TNF-α and IL-1β, which are elevated in neurodegenerative diseases
*IL1β↓,
*PI3K↑, apigenin has been shown to activate the PI3K/Akt signaling pathway, which is involved in promoting neuronal survival and preventing apoptosis.
*Akt↑,
*BBB↑, Apigenin has additional neuroprotective properties due to its ability to cross the BBB and enter the brain
*NRF2↑, figure 1
*SOD↑, pigenin has also been shown to activate various antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx)
*GPx↑,
*MAPK↓, Apigenin inhibits the MAPK signalling system, which significantly reduces oxidative stress-induced damage in the brain
*Catalase↑, , including SOD, catalase, GPx and heme oxygenase-1 (HO-1) [37].
*HO-1↑,
*COX2↓, apigenin has the ability to inhibit the expression and function of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2), enzymes that produce inflammatory mediators
*PGE2↓,
*PPARγ↑, apigenin has the ability to inhibit the expression and function of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2), enzymes that produce inflammatory mediators
*TLR4↓,
*GSK‐3β↓, Apigenin can inhibit the activity of GSK-3β,
*Aβ↓, Inhibiting GSK-3 can reduce Aβ production and prevent neurofibrillary disorders.
*NLRP3↓, Apigenin suppresses nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation by upregulating PPAR-γ
*BDNF↑, Apigenin causes upregulation of BDNF and TrkB expression in several animal models
*TrkB↑,
*GABA↑, Apigenin enhances GABAergic signaling by increasing the frequency of chloride channel opening, leading to increased inhibitory neurotransmission
*AChE↓, It blocks acetylcholinesterase and increases acetylcholine availability.
*Ach↑,
*5HT↑, Apigenin has been shown to increase 5-HT levels, decrease 5-HT turnover, and prevent dopamine changes.
*cognitive↑, Apigenin increases the availability of acetylcholine in the synapse after inhibiting AChE, thereby enhancing cholinergic neurotransmission and improving cognitive function and memory
*MAOA↓, apigenin acts as a monoamine oxidase (MAO) inhibitor and MAO inhibitors increase the levels of monoamines in the brain

1548- Api,    A comprehensive view on the apigenin impact on colorectal cancer: Focusing on cellular and molecular mechanisms
- Review, Colon, NA
*BioAv↓, Apigenin is not easily absorbed orally because of its low water solubility, which is only 2.16 g/mL
*Half-Life∅, Apigenin is slowly absorbed and eliminated from the body, as evidenced by its half‐life of 91.8 h in the blood
selectivity↑, selective anticancer effects and effective cell cytotoxic activity while exhibiting negligible toxicity to ordinary cells
*toxicity↓, intentional consumption in higher doses, as the toxicity hazard is low
Wnt/(β-catenin)↓, inhibiting the Wnt/β‐catenin
P53↑,
P21↑,
PI3K↓,
Akt↓,
mTOR↓,
TumCCA↑, G2/M
TumCI↓,
TumCMig↓,
STAT3↓, apigenin can activate p53, which improves catalase and inhibits STAT3,
PKM2↓,
EMT↓, reversing increases in epithelial–mesenchymal transition (EMT)
cl‑PARP↑, apigenin increases the cleavage of poly‐(ADP‐ribose) polymerase (PARP) and rapidly enhances caspase‐3 activity,
Casp3↑,
Bax:Bcl2↑,
VEGF↓, apigenin suppresses VEGF transcription
Hif1a↓, decrease in hypoxia‐inducible factor 1‐alpha (HIF‐1α
Dose∅, effectiveness of apigenin (200 and 300 mg/kg) in treating CC was evaluated by establishing xenografts on Balb/c nude mice.
GLUT1↓, Apigenin has been found to inhibit GLUT1 activity and glucose uptake in human pancreatic cancer cells
GlucoseCon↓,

1547- Api,    Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading
- Review, NA, NA
angioG↓,
EMT↓,
CSCs↓,
TumCCA↑,
Dose∅, Dried parsley 45,035ug/g: Dried chamomille flower 3000–5000ug/g: Parsley 2154.6ug/g:
ROS↑, activity of Apigenin has been linked to the induction of oxidative stress in cancer cells
MMP↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity
Catalase↓, catalase and glutathione (GSH), molecules involved in alleviating oxidative stress, were downregulated after Apigenin
GSH↓,
PI3K↓, suppression of the PI3K/Akt and NF-κB
Akt↓,
NF-kB↓,
OCT4↓, glycosylated form of Apigenin (i.e., Vitexin) was able to suppress stemness features of human endometrial cancer, as documented by the downregulation of Oct4 and Nanog
Nanog↓,
SIRT3↓, inhibition of sirtuin-3 (SIRT3) and sirtuin-6 (SIRT6) protein levels
SIRT6↓,
eff↑, ability of Apigenin to interfere with CSC features is often enhanced by the co-administration of other flavonoids, such as chrysin
eff↑, Apigenin combined with a chemotherapy agent, temozolomide (TMZ), was used on glioblastoma cells and showed better performance in cell arrest at the G2 phase compared with Apigenin or TMZ alone,
Cyt‑c↑, release of cytochrome c (Cyt c)
Bax:Bcl2↑, Apigenin has been shown to induce the apoptosis death pathway by increasing the Bax/Bcl-2 ratio
p‑GSK‐3β↓, Apigenin has been shown to prevent activation of phosphorylation of glycogen synthase kinase-3 beta (GSK-3β)
FOXO3↑, Apigenin administration increased the expression of forkhead box O3 (FOXO3)
p‑STAT3↓, Apigenin can induce apoptosis via inhibition of STAT3 phosphorylation
MMP2↓, downregulation of the expression of MMP-2 and MMP-9
MMP9↓,
COX2↓, downregulation of PI3K/Akt in leukemia HL60 cells [156,157] and of COX2, iNOS, and reactive oxygen species (ROS) accumulation in breast cancer cells
MMPs↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity, as proved by low MMP in Apigenin-treated cells
NRF2↓, suppressed the nuclear factor erythroid 2-related factor 2 (Nrf2)
HDAC↓, inhibition of histone deacetylases (HDACs) is the mechanism through which Apigenin induces apoptosis in prostate cancer cells
Telomerase↓, Apigenin has been shown to downregulate telomerase activity
eff↑, Indeed, co-administration with 5-fluorouracil (5-FU) increased the efficacy of Apigenin in human colon cancer through p53 upregulation and ROS accumulation
eff↑, Apigenin synergistically enhances the cytotoxic effects of Sorafenib
eff↑, pretreatment of pancreatic BxPC-3 cells for 24 h with a low concentration of Apigenin and gemcitabine caused the inhibition of the GSK-3β/NF-κB signaling pathway, leading to the induction of apoptosis
eff↑, In NSCLC cells, compared to monotherapy, co-treatment with Apigenin and naringenin increased the apoptotic rate through ROS accumulation, Bax/Bcl-2 increase, caspase-3 activation, and mitochondrial dysfunction
eff↑, Several studies have shown that Apigenin-induced autophagy may play a pro-survival role in cancer therapy; in fact, inhibition of autophagy has been shown to exacerbate the toxicity of Apigenin
XIAP↓,
survivin↓,
CK2↓,
HSP90↓,
Hif1a↓,
FAK↓,
EMT↓,

1565- Api,    Apigenin-7-glucoside induces apoptosis and ROS accumulation in lung cancer cells, and inhibits PI3K/Akt/mTOR pathway
- in-vitro, Lung, A549 - in-vitro, Nor, BEAS-2B - in-vitro, Lung, H1975
TumCP↓, AGL significantly reduced proliferation, promoted cell apoptosis, and attenuated the migration and invasion of A549 or H1975 cell
Apoptosis↑,
TumCMig↓,
TumCI↓,
Cyt‑c↑, elevated the levels of cytochrome C and MDA
MDA↑,
GSH↓, but reduced the production of GSH in A549 and H1975 cells.
ROS↑, AGL enhanced the accumulation of ROS
PI3K↓, induces ROS accumulation in lung cancer cells by repressing PI3K/Akt/mTOR pathway
Akt↓,
mTOR↓,

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

1560- Api,    Apigenin as an anticancer agent
- Review, NA, NA
Apoptosis↑,
Casp3∅,
Casp8∅,
TNF-α∅,
Cyt‑c↑, evidenced by the induction of cytochrome c
MMP2↓, Apigenin treatment leads to significant downregulation of matrix metallopeptidases-2, -9, Snail, and Slug,
MMP9↓,
Snail↓,
Slug↓,
NF-kB↓, NF-κB p105/p50, PI3K, Akt, and the phosphorylation of p-Akt decreases after treatment
p50↓,
PI3K↓,
Akt↓,
p‑Akt↓,

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

2593- Api,    Apigenin promotes apoptosis of 4T1 cells through PI3K/AKT/Nrf2 pathway and improves tumor immune microenvironment in vivo
- in-vivo, BC, 4T1
TumCP↓, API suppresses 4T1 cells proliferation
TumCMig↓, API restraints 4T1 cells migration and invasion
TumCI↓,
Apoptosis↑, API triggers 4T1 apoptosis and modulates the expression levels of apoptotic-associated proteins in 4T1 cells
MMP↑, API triggers the depolarization of ΔΨm in 4T1 cells
ROS↑, API induces ROS generation
p‑PI3K↓, The results revealed a significant downregulation of p-PI3K/PI3K, p-AKT/AKT, and Nrf2 in 4T1 cells following API treatment
PI3K↓,
Akt↓,
NRF2↓,
AntiTum↑, API exhibits anti-tumor activity in mice
OS↑, results of animal survival experiments show that API can appropriately prolong the survival of mice with mammary gland tumors

2584- Api,  Chemo,    The versatility of apigenin: Especially as a chemopreventive agent for cancer
- Review, Var, NA
ChemoSen↑, Apigenin has also been studied for its potential as a sensitizer in cancer therapy, improving the efficacy of traditional chemotherapeutic drugs and radiotherapy
RadioS↑, Apigenin enhances radiotherapy effects by sensitizing cancer cells to radiation-induced cell death
eff↝, It works by suppressing the expression of involucrin (hINV), a hallmark of keratinocyte development. Apigenin inhibits the rise in hINV expression caused by differentiating agents
DR5↑, Apigenin also greatly upregulates the expression of death receptor 5 (DR5
selectivity↑, Surprisingly, apigenin-mediated increase of DR5 expression is missing in normal mononuclear cells from human peripheral blood and doesn't subject these cells to TRAIL-induced death.
angioG↓, Apigenin has been found to prevent angiogenesis by targeting critical signaling pathways involved in blood vessel creation.
selectivity↑, Importantly, apigenin has been demonstrated to selectively kill cancer cells while sparing normal ones
chemoP↑, This selective cytotoxicity is beneficial in cancer therapy because it reduces the negative effects frequently associated with traditional treatments like chemotherapy
MAPK↓, Apigenin's ability to suppress MAPK signaling adds to its anticancer properties.
PI3K↓, Apigenin suppresses the PI3K/Akt/mTOR pathway, which is typically dysregulated in cancer.
Akt↓,
mTOR↓,
Wnt↓, Apigenin inhibits Wnt signaling by increasing β-catenin degradation
β-catenin/ZEB1↓,
GLUT1↓, fig 3
radioP↑, while reducing radiation-induced damage to healthy tissues
BioAv↓, obstacles associated with apigenin's low bioavailability and stability
chemoPv↑, Especially as a chemopreventive agent for cancer

2318- Api,    Apigenin as a multifaceted antifibrotic agent: Therapeutic potential across organ systems
- Review, Nor, NA
*ROS↓, Apigenin reduces fibrosis by targeting oxidative stress, fibroblast activation, and ECM buildup across organs
*PKM2↓, PKM2-HIF-1α pathway inhibited
*Hif1a↓,
*TGF-β↓, apigenin suppresses the PKM2-HIF-1α and TGF-β signaling pathways to prevent fibrosis
*AMPK↑, In the kidneys, it activates AMPK to suppress TGF-β1-induced fibroblast transformation
*Inflam↓, For the brain, apigenin reduces inflammation and oxidative stress through the PI3K/Akt/Nrf2 pathway.
*PI3K↓, Apigenin exerts neuroprotective effects in neonatal hypoxic-ischemic (HI) brain injury by activating the PI3K/Akt/Nrf2 signaling pathway, which is critical in defending neurons from oxidative stress and inflammation.
*Akt↑,
*NRF2↑, apigenin reduces oxidative damage through Nrf2 and NF-κB pathway modulation
*NF-kB↓, downregulates critical TGF-β and NF-κB pathways.

269- Api,    Cytotoxicity of apigenin on leukemia cell lines: implications for prevention and therapy
- in-vitro, AML, HL-60 - in-vitro, AML, K562 - in-vitro, AML, TF1
JAK↓,
PI3K↓, PI3K/PKB
cDC2↓,
STAT↓,

240- Api,    The flavonoid apigenin reduces prostate cancer CD44(+) stem cell survival and migration through PI3K/Akt/NF-κB signaling
- in-vitro, Pca, PC3 - in-vitro, Pca, CD44+
P21↑,
p27↑,
Casp3↑,
Casp8↑,
Slug↓,
Snail↓,
NF-kB↓,
PI3K↓,
Akt↓,

3383- ART/DHA,    Dihydroartemisinin: A Potential Natural Anticancer Drug
- Review, Var, NA
TumCP↓, DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stres
Apoptosis↑,
TumMeta↓,
angioG↓,
TumAuto↑,
ER Stress↑,
ROS↑, DHA could increase the level of ROS in cells, thereby exerting a cytotoxic effect in cancer cells
Ca+2↑, activation of Ca2+ and p38 was also observed in DHA-induced apoptosis of PC14 lung cancer cells
p38↑,
HSP70/HSPA5↓, down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA
PPARγ↑, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ)
GLUT1↓, DHA was shown to inhibit the activity of glucose transporter-1 (GLUT1) and glycolytic pathway by inhibiting phosphatidyl-inositol-3-kinase (PI3K)/AKT pathway and downregulating the expression of hypoxia inducible factor-1α (HIF-1α)
Glycolysis↓, Inhibited glycolysis
PI3K↓,
Akt↓,
Hif1a↓,
PKM2↓, DHA could inhibit the expression of PKM2 as well as inhibit lactic acid production and glucose uptake, thereby promoting the apoptosis of esophageal cancer cells
lactateProd↓,
GlucoseCon↓,
EMT↓, regulating the EMT-related genes (Slug, ZEB1, ZEB2 and Twist)
Slug↓, Downregulated Slug, ZEB1, ZEB2 and Twist in mRNA level
Zeb1↓,
ZEB2↓,
Twist↓,
Snail?, downregulated the expression of Snail and PI3K/AKT signaling pathway, thereby inhibiting metastasis
CAFs/TAFs↓, DHA suppressed the activation of cancer-associated fibroblasts (CAFs) and mouse cancer-associated fibroblasts (L-929-CAFs) by inhibiting transforming growth factor-β (TGF-β signaling
TGF-β↓,
p‑STAT3↓, blocking the phosphorylation of STAT3 and polarization of M2 macrophages
M2 MC↓,
uPA↓, DHA could inhibit the growth and migration of breast cancer cells by inhibiting the expression of uPA
HH↓, via inhibiting the hedgehog signaling pathway
AXL↓, DHA acted as an Axl inhibitor in prostate cancer, blocking the expression of Axl through the miR-34a/miR-7/JARID2 pathway, thereby inhibiting the proliferation, migration and invasion of prostate cancer cells.
VEGFR2↓, inhibition of VEGFR2-mediated angiogenesis
JNK↑, JNK pathway activated and Beclin 1 expression upregulated.
Beclin-1↑,
GRP78/BiP↑, Glucose regulatory protein 78 (GRP78, an ER stress-related molecule) was upregulated after DHA treatment.
eff↑, results demonstrated that DHA-induced ER stress required iron
eff↑, DHA was used in combination with PDGFRα inhibitors (sunitinib and sorafenib), it could sensitize ovarian cancer cells to PDGFR inhibitors and achieved effective therapeutic efficacy
eff↑, DHA combined with 2DG (a glycolysis inhibitor) synergistically induced apoptosis through both exogenous and endogenous apoptotic pathways
eff↑, histone deacetylase inhibitors (HDACis) enhanced the anti-tumor effect of DHA by inducing apoptosis.
eff↑, DHA enhanced PDT-induced cell growth inhibition and apoptosis, increased the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway
eff↑, DHA was added to magnetic nanoparticles (MNP), and the MNP-DHA has shown an effect in the treatment of intractable breast cancer
IL4↓, downregulated IL-4;
DR5↑, Upregulated DR5 in protein, Increased DR5 promoter activity
Cyt‑c↑, Released cytochrome c from the mitochondria to the cytosol
Fas↑, Upregulated fas, FADD, Bax, cleaved-PARP
FADD↑,
cl‑PARP↑,
cycE/CCNE↓, Downregulated Bcl-2, Bcl-xL, procaspase-3, Cyclin E, CDK2 and CDK4
CDK2↓,
CDK4↓,
Mcl-1↓, Downregulated Mcl-1
Ki-67↓, Downregulated Ki-67 and Bcl-2
Bcl-2↓,
CDK6↓, Downregulated of Cyclin E, CDK2, CDK4 and CDK6
VEGF↓, Downregulated VEGF, COX-2 and MMP-9
COX2↓,
MMP9↓,

4993- ART/DHA,    Dihydroartemisinin inhibits galectin-1–induced ferroptosis resistance and peritoneal metastasis of gastric cancer via the Nrf2–HO-1 pathway
- vitro+vivo, GC, NA
Ferroptosis↑, DHA suppresses galectin-1-promoted GCPM via the PI3K/Akt/Nrf2/HO-1 pathway in vitro
NRF2↓, DHA promotes ferroptosis by downregulating Nrf2/HO-1
HO-1↓,
PI3K↓, We found that DHA significantly affected galectin-1 expression and inhibited PI3K/Akt activation
Akt↓,
TumMeta↓, DHA inhibits peritoneal metastasis through the PI3K/Akt/Nrf2/HO-1 pathway in vivo

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↓,

5405- ASA,    Exploring Aspirin’s Potential in Cancer Prevention: A Comprehensive Review of the Current Evidence
- Review, Var, NA
Risk↓, emerging evidence suggests that aspirin may reduce the risk of certain cancers, particularly colorectal cancer (CRC).
COX1↓, Aspirin’s anticancer effects are primarily attributed to its cyclooxygenase (COX) enzyme inhibition, which decreases prostaglandin E2 (PGE2) levels and disrupts cancer-related signaling pathways.
PGE2↓,
Inflam↓, Aspirin is a versatile medication commonly used as an analgesic, anti-inflammatory, antipyretic, and antiplatelet agent [2,3].
*AntiAg↓,
PI3K↓, By irreversibly inhibiting COX-2, aspirin reduces PGE2 levels, thereby decreasing the activation of cancer-related signaling pathways such as PI3K/AKT (phosphatidylinositol 3-kinase/protein kinase B) and ERK and promoting apoptosis in cancer cells ​
Akt↓,
Risk↓, For pancreatic cancer, aspirin for at least five years significantly reduces the risk of death, though this protective effect becomes apparent only after a five-year lag period [39].

3156- Ash,    Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug
- Review, Var, NA
MAPK↑, Figure 3
p38↑,
BAX↑,
BIM↑,
CHOP↑,
ROS↑,
DR5↑,
Apoptosis↑,
Ferroptosis↑,
GPx4↓,
BioAv↝, WA has a rapid oral absorption and reaches to peak plasma concentration of around 16.69 ± 4.02 ng/ml within 10 min after oral administration of Withania somnifera aqueous extract at dose of 1000 mg/kg, which is equivalent to 0.458 mg/kg of WA
HSP90↓, table 1 10uM) were found to inhibit the chaperone activity of HSP90
RET↓,
E6↓,
E7↓,
Akt↓,
cMET↓,
Glycolysis↓, by suppressing the glycolysis and tricarboxylic (TCA) cycle
TCA↓,
NOTCH1↓,
STAT3↓,
AP-1↓,
PI3K↓,
eIF2α↓,
HO-1↑,
TumCCA↑, WA (1--3 uM) have been reported to inhibit cell proliferation by inducing G2 and M phase cycle arrest inovarian, breast, prostate, gastric and myelodysplastic/leukemic cancer cells and osteosarcoma
CDK1↓, WA is able to decrease the cyclin-dependent kinase 1 (Cdk1) activity and prevent Cdk1/cyclin B1 complex formation, which are key steps in cell cycle progression
*hepatoP↑, A treatment (40 mg/kg) reduces acetaminophen-induced liver injury (AILI) in mouse models and decreases H 2O 2-induced glutathione (GSH) depletion and necrosis in hepatocyte
*GSH↑,
*NRF2↑, WA triggers an anti-oxidant response after acetaminophen overdose by enhancing hepatic transcription of the nuclear factor erythroid 2–related factor 2 (NRF2)-responsive gene
Wnt↓, indirectly inhibit Wnt
EMT↓, WA can also block tumor metastasis through reduced expression of epithelial mesenchymal transition (EMT) markers.
uPA↓, WA (700 nM) exert anti-meta-static activities in breast cancer cells through inhibition of the urokinase-type plasminogen activator (uPA) protease
CSCs↓, s WA (125-500 nM) suppress tumor sphere formation indicating that the self-renewal of CSC is abolished
Nanog↓, loss of these CSC-specific characteristics is reflected in the loss of typical stem cell markers such as ALDH1A, Nanog, Sox2, CD44 and CD24
SOX2↓,
CD44↓,
lactateProd↓, drop in lactate levels compared to control mice.
Iron↑, Furthermore, we found that WA elevates the levels of intracellular labile ferrous iron (Fe +2 ) through excessive activation of heme oxygenase-1 (HMOX1), which independently causes accumulation of toxic lipid radicals and ensuing ferroptosis
NF-kB↓, nhibition of NF-kB kinase signaling pathway

3166- Ash,    Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives
- Review, Var, NA
*p‑PPARγ↓, preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ)
*cardioP↑, cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis.
*AMPK↑,
*BioAv↝, The oral bioavailability was found to be 32.4 ± 4.8% after 5 mg/kg intravenous and 10 mg/kg oral WA administration.
*Half-Life↝, The stability studies of WA in gastric fluid, liver microsomes, and intestinal microflora solution showed similar results in male rats and humans with a half-life of 5.6 min.
*Half-Life↝, WA reduced quickly, and 27.1% left within 1 h
*Dose↑, WA showed that formulation at dose 4800 mg having equivalent to 216 mg of WA, was tolerated well without showing any dose-limiting toxicity.
*chemoPv↑, Here, we discuss the chemo-preventive effects of WA on multiple organs.
IL6↓, attenuates IL-6 in inducible (MCF-7 and MDA-MB-231)
STAT3↓, WA displayed downregulation of STAT3 transcriptional activity
ROS↓, associated with reactive oxygen species (ROS) generation, resulted in apoptosis of cells. The WA treatment decreases the oxidative phosphorylation
OXPHOS↓,
PCNA↓, uppresses human breast cells’ proliferation by decreasing the proliferating cell nuclear antigen (PCNA) expression
LDH↓, WA treatment decreases the lactate dehydrogenase (LDH) expression, increases AMP protein kinase activation, and reduces adenosine triphosphate
AMPK↑,
TumCCA↑, (SKOV3 andCaOV3), WA arrest the G2/M phase cell cycle
NOTCH3↓, It downregulated the Notch-3/Akt/Bcl-2 signaling mediated cell survival, thereby causing caspase-3 stimulation, which induces apoptosis.
Akt↓,
Bcl-2↓,
Casp3↑,
Apoptosis↑,
eff↑, Withaferin-A, combined with doxorubicin, and cisplatin at suboptimal dose generates ROS and causes cell death
NF-kB↓, reduces the cytosolic and nuclear levels of NF-κB-related phospho-p65 cytokines in xenografted tumors
CSCs↓, WA can be used as a pharmaceutical agent that effectively kills cancer stem cells (CSCs).
HSP90↓, WA inhibit Hsp90 chaperone activity, disrupting Hsp90 client proteins, thus showing antiproliferative effects
PI3K↓, WA inhibited PI3K/AKT pathway.
FOXO3↑, Par-4 and FOXO3A proapoptotic proteins were increased in Pten-KO mice supplemented with WA.
β-catenin/ZEB1↓, decreased pAKT expression and the β-catenin and N-cadherin epithelial-to-mesenchymal transition markers in WA-treated tumors control
N-cadherin↓,
EMT↓,
FASN↓, WA intraperitoneal administration (0.1 mg) resulted in significant suppression of circulatory free fatty acid and fatty acid synthase expression, ATP citrate lyase,
ACLY↓,
ROS↑, WA generates ROS followed by the activation of Nrf2, HO-1, NQO1 pathways, and upregulating the expression of the c-Jun-N-terminal kinase (JNK)
NRF2↑,
HO-1↑,
NQO1↑,
JNK↑,
mTOR↓, suppressing the mTOR/STAT3 pathway
neuroP↑, neuroprotective ability of WA (50 mg/kg b.w)
*TNF-α↓, WA attenuate the levels of neuroinflammatory mediators (TNF-α, IL-1β, and IL-6)
*IL1β↓,
*IL6↓,
*IL8↓, WA decreases the pro-inflammatory cytokines (IL-6, TNFα, IL-8, IL-18)
*IL18↓,
RadioS↑, radiosensitizing combination effect of WA and hyperthermia (HT) or radiotherapy (RT)
eff↑, WA and cisplatin at suboptimal dose generates ROS and causes cell death [41]. The actions of this combination is attributed by eradicating cells, revealing markers of cancer stem cells like CD34, CD44, Oct4, CD24, and CD117

5389- AsP,  Tras,    ASCORBYL PALMITATE ENHANCES ANTI-PROLIFERATIVE EFFECT OF TRASTUZUMAB IN HER2-POSITIVE BREAST CANCER CELLS
tumCV↓, AP reduced cell viability in a time- and dose-dependent manner, and its combination with trastuzumab further decreased cell viability.
eff↑, A cytometric analysis showed enhanced apoptosis after combination treatment
P53↑, mRNA analysis revealed upregulated TP53 mRNA expression, along with upregulation of BAX, CYCS, CASP3, and CASP8 gene expression, while the BCL-2 and BCL2L1 genes were downregulated, further supporting the induction of apoptosis.
BAX↑,
Casp3↑,
Casp8↑,
Bcl-2↓,
Apoptosis↑,
p‑p38↓, Western blot assay, which showed suppression of phospho-P38, ERK1/2, and PI3K protein synthesis.
ERK↓,
PI3K↓,

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

4804- ASTX,    Astaxanthin in cancer therapy and prevention (Review)
- Review, Var, NA - Review, AD, NA
*antiOx↑, gained significant attention for its potent antioxidant, anti-inflammatory and anti-proliferative properties.
*Inflam↓,
ChemoSen⇅, In some instances, it reduces the cytotoxicity of cisplatin, particularly with cisplatin on the SKBR3 breast cancer cell line, indicating a potential protective effect. In certain cases, AXT enhances the cytotoxic effect of the chemotherapy drugs
chemoP↑, The present review detailed both in vitro and in vivo studies highlighting the effectiveness of AXT in sensitizing cancer cells to chemotherapy, thereby enhancing therapeutic outcomes and potentially reducing treatment-related side effects.
BioAv↑, incorporation of AXT in nanoparticle-based delivery systems has further improved its bioavailability
TumCP↑, AXT exhibits hormetic effects on U251-MG, T98G and CRT-MG cell lines, where low doses stimulate cell proliferation
ROS⇅, while higher doses induce apoptosis by triggering a dose-dependent oxidative stress response, significantly increasing reactive oxygen species (ROS) levels and promoting apoptosis
Apoptosis↑,
PI3K↑, AXT activates the PI3K/Akt/GSK3β pathway, leading to the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor, in SH-SY5Y cells under oxygen and glucose deprivation conditions
Akt↑,
GSK‐3β↑,
NRF2↑,
AntiCan↑, antioxidant, AXT has the potential to act as both an anticancer drug and a neuroprotectant.
*neuroP↑, AXT protects against oxidative stress, which causes mitochondrial dysfunction and apoptosis, thereby reducing the detrimental effects associated with neurodegenerative diseases such as Alzheimer's, Parkinson's
eff↑, The synergistic cytotoxic effect of AXT with melatonin showed enhanced efficacy in the T47D cell line compared with the MDA-MB-231 line
AntiTum↑, AXT effectively reduced tumor size and the number of cancer cells in mice, supporting its potential anti-tumor activity.

4812- ASTX,    Astaxanthin suppresses the metastasis of colon cancer by inhibiting the MYC-mediated downregulation of microRNA-29a-3p and microRNA-200a
- in-vitro, CRC, HCT116
miR-29b↑, AXT increases miR-29a-3p and miR-200a expression, and thereby suppresses the expression of MMP2 and ZEB1, respectively.
miR-200b↑,
MMP2↓, Astaxanthin suppresses MMP2 activity through upregulation of miR-29a-3p
Zeb1↓,
EMT↓, As a result, AXT represses the epithelial-mesenchymal transition (EMT) of CRC cells.
Apoptosis↑, AXT suppresses oral carcinomas by inducing apoptosis through the inhibition of Erk/MAPK and PI3K/Akt signaling
ERK↓,
MAPK↓,
PI3K↓,
Akt↓,
MMPs↓, AXT reduces the metastasis of cancer cells by decreasing the expression of MMPs,
TumMeta↓, Astaxanthin suppresses the metastatic activity of colon cancer cell in in vivo model

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

5505- Ba,    Baicalein inhibits the progression of thyroid cancer by suppressing the TPL2/MEK2/ERK2 pathway
- in-vitro, Thyroid, NA
ERK↓, BA has also anti-tumor effects on TC, inhibiting the ERK1/2 and PI3K/Akt pathways to induce the apoptosis and autophagy in TC cells (16, 17)
PI3K↓,
Akt↓,
Apoptosis↑,
TumAuto↑,
NF-kB↑, Our previous research suggested that BA activates the NF-κB signaling pathway to induce the autophagy and apoptosis
MEK↓, BA modulates PLAU expression via inhibiting TPL2/MEK2/ERK2 pathway to regulate Golgi apparatus reprogramming

5502- Ba,    An overview of pharmacological activities of baicalin and its aglycone baicalein: New insights into molecular mechanisms and signaling pathways
- Review, Var, NA
*AntiCan↑, antibacterial, antiviral, anticancer, anticonvulsant, anti-oxidant, hepatoprotective, and neuroprotective effects.
*antiOx↑,
*hepatoP↑,
*neuroP↑,
*ROS↓, pharmacological properties of baicalin and baicalein are due to their abilities to scavenge reactive oxygen species (ROS)
Ca+2↑, Baicalein mainly induced apoptosis through Ca+2 influx via Ca2+ release from the reticulum to cytosol dependent on phospholipase C protein
ROS↑, ROS production is associated with baicalein-induced apoptosis via Ca2+-dependent apoptosis in tongue and breast cancer cells (78, 79)
BAX↑, The level of Bax/Bcl-2 increased and caspase-3 and -9 were activated following the release of cytochrome C (80).
Casp3↑,
Casp9↑,
Cyt‑c↑,
MMP↓, In gastric cancer cells, baicalein mediated apoptosis in a dose-dependent manner through disruption of mitochondrial membrane potential
Mcl-1↓, In pancreatic cancer cells, baicalein induced apoptosis via suppression of the Mcl-1 protein.
PI3K↓, In HepG2 cells, baicalin-copper induced apoptosis through down-regulation of phosphoinositide-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway
Akt↓,
mTOR↓,
BAD↓, Studies demonstrated that baicalein treatment suppressed Bad, ERK1/2 phosphorylation, and MEK1 expression both in vitro and in vivo.
ERK↓,
MEK↓,
DR5↑, Baicalein enhanced the activity of death receptor-5 (DR5) in prostate cancer PC3 cells.
Fas↑, baicalin is the active ingredient that acts as Fas ligand and caused up-regulation of Fas protein (89).
TumMeta↓, Baicalin/baicalein not only induced apoptosis in cancer cells but also suppressed metastasis.
EMT↓, both baicalin and baicalein inhibited epithelial-mesenchymal transition (EMT) through the suppression of TGF-β in breast epithelial cells through the NF-κB pathway (92).
SMAD4↓, baicalein suppressed metastasis in gastric cancer through inactivation of the Smad4/TGF-β pathway (93).
TGF-β↓,
MMP9↓, baicalin and baicalein inhibition of the expression level of matrix metalloproteinases (MMP) such as MMP-9 and MMP-2 in liver, breast, lung, ovarian, gastric, and colorectal cancers and glioma
MMP2↓,
HIF-1↓, Baicalin attenuated lung metastasis through inhibition of hypoxia-inducible factor (HIF)
12LOX↓, Baicalein acts as an anticancer agent via inhibiting 12-lipooxygenase (12-LOX),

5501- Ba,    Therapeutic effects and mechanisms of action of Baicalein on stomach cancer: a comprehensive systematic literature review
- Review, GC, NA
AntiCan↑, The review demonstrated that BC exerts therapeutic effects on GC through multiple biochemical mechanisms.
Apoptosis↑, BC plays an important role in inducing apoptosis, inhibiting cell proliferation, and suppressing metastasis in GC cells.
TumCP↓,
TumMeta↓,
BAX↑, graphical abstract
TumAuto↑,
ROS↑,
NRF2↝, BC induced apoptosis and autophagy in MGC-803, SGC-7901, and HGC-27 cells, enhancing cisplatin sensitivity via suppression of the AKT/mTOR pathway and modulation of the Nrf2/Keap1 axis.
PI3K↓,
Akt↓,
NF-kB↓,
TGF-β↓,
SMAD4↓,
GPx4↓, It induces autophagy and ferroptosis, partly through p53 activation and suppression of SLC7A11/GPX4, and disrupts mitochondrial membrane potential via reactive oxygen species (ROS) generation [31, 37]
MMP↓,
*HO-1↑, BC stabilizes Nrf2, leading to the induction of antioxidant enzymes such as HO-1, GST, and NQO1, which mitigate oxidative stress and contribute to its antitumor effects [38].
*GSTs↑,
*antiOx↑,
*AntiTum↑,
*NRF2↑,
ChemoSen↑, BC induced apoptosis and autophagy in MGC-803, SGC-7901, and HGC-27 cells, enhancing cisplatin sensitivity via suppression of the AKT/mTOR pathway and modulation of the Nrf2/Keap1 axis.
Akt↓,
mTOR↓,
FAK↓, reducing FAK expression
Ki-67↓, Immunohistochemical analysis also revealed lower Ki-67 levels, indicating reduced cellular proliferation.

4276- BA,    Baicalin Attenuates Oxygen–Glucose Deprivation/Reoxygenation–Induced Injury by Modulating the BDNF-TrkB/PI3K/Akt and MAPK/Erk1/2 Signaling Axes in Neuron–Astrocyte Cocultures
- in-vivo, Stroke, NA
*BDNF↑, has been indicated to protect neurons by promoting brain-derived neurotrophic factor (BDNF).
*neuroP↑, neuroprotective mechanisms of baicalin against oxygen–glucose deprivation/reoxygenation
*TrkB↑, baicalin significantly increased the expressions of TrkB, PI3K/AKT, and MAPK/ERK.
*PI3K↑,
*Akt↑,
*MAPK↑,
*ERK↑,
*NO↓, elevation of NO and MDA was significantly attenuated by BCL treatment.
*MDA↓,
*SOD↑, BCL treatment increased the expression level of SOD
*TNF-α↓, OGD/R treatment significantly increased the expression levels of TNF-α, IL-1β, and IL-6 (p < 0.01). Compared with that in the OGD/R group, BCL robustly reduced the release of inflammatory cytokines
*IL1β↓,
*IL6?,

1532- Ba,    Baicalein as Promising Anticancer Agent: A Comprehensive Analysis on Molecular Mechanisms and Therapeutic Perspectives
- Review, NA, NA
ROS↑, Baicalein initially incited the formation of ROS, which subsequently aimed at endoplasmic reticulum stress and stimulated the Ca2+/-reliant mitochondrial death pathway.
ER Stress↑,
Ca+2↑,
MMPs↓,
Cyt‑c↑, cytochrome C release
Casp3↑,
ROS↑, Baicalein on apoptosis in human bladder cancer 5637 cells was investigated, and it was found that it induces ROS generation
DR5↑, Baicalein activates DR5 up-regulation
ROS↑, MCF-7 cells by inducing mitochondrial apoptotic cell death. It does this by producing ROS, such as hydroxyl radicals, and reducing Cu (II) to Cu (I) in the Baicalein–Cu (II) system
BAX↑,
Bcl-2↓,
MMP↓,
Casp3↑,
Casp9↑,
P53↑,
p16↑,
P21↑,
p27↑,
HDAC10↑, modulating the up-regulation of miR-3178 and Histone deacetylase 10 (HDAC10), which accelerates apoptotic cell death
MDM2↓, MDM2-mediated breakdown
Apoptosis↑,
PI3K↓, baicalein-influenced apoptosis is controlled via suppression of the PI3K/AKT axis
Akt↓,
p‑Akt↓, by reducing the concentrations of p-Akt, p-mTOR, NF-κB, and p-IκB while increasing IκB expression
p‑mTOR↓,
NF-kB↓,
p‑IκB↓,
IκB↑,
BAX↑,
Bcl-2↓,
ROS⇅, Based on its metabolic activities and intensity, Baicalein can act as an antioxidant and pro-oxidant.
BNIP3↑, Baicalein also increases the production of BNIP3 which is a protein stimulated by ROS and promotes apoptosis
p38↑,
12LOX↓, inhibition of 12-LOX (Platelet-type 12-Lipoxygenase)
Mcl-1↓,
Wnt?, decreasing Wnt activity
GLI2↓, Baicalein significantly reduced the presence of Gli-2, a crucial transcription factor in the SHH pathway
AR↓, downregulating the androgen receptor (AR)
eff↑, PTX/BAI NE could increase intracellular ROS levels, reduce cellular glutathione (GSH) levels, and trigger caspase-3 dynamism in MCF-7/Tax cells. Moreover, it exhibited higher efficacy in inhibiting tumors in vivo

1525- Ba,  almon,    Synergistic antitumor activity of baicalein combined with almonertinib in almonertinib-resistant non-small cell lung cancer cells through the reactive oxygen species-mediated PI3K/Akt pathway
- in-vitro, Lung, H1975 - in-vivo, Lung, NA
eff↑, Compared with baicalein or almonertinib alone, the combined application of the two drugs dramatically attenuates cell proliferation
TumCP↓,
Apoptosis↑,
cl‑Casp3↑,
cl‑PARP↑,
cl‑Casp9↑,
p‑PI3K↓, combination of baicalein and almonertinib can improve the antitumor activity in almonertinib-resistant NSCLC through the ROS-mediated PI3K/Akt pathway.
p‑Akt↓,
ROS↑, baicalein combined with almonertinib results in massive accumulation of reactive oxygen species (ROS)
eff↓, preincubation with N-acetyl-L-cysteine (ROS remover) prevents proliferation as well as inhibits apoptosis induction

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


Showing Research Papers: 1 to 50 of 281
Page 1 of 6 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 281

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   Catalase↓, 1,   Ferroptosis↑, 4,   GPx4↓, 4,   GSH↓, 4,   HO-1↓, 1,   HO-1↑, 2,   Iron↑, 1,   c-Iron↑, 1,   lipid-P↑, 2,   MDA↑, 2,   NQO1↑, 1,   NRF2↓, 4,   NRF2↑, 2,   NRF2↝, 1,   OSI↑, 1,   OXPHOS↓, 1,   ROS↓, 1,   ROS↑, 24,   ROS⇅, 3,   SIRT3↓, 1,   SOD↓, 1,   TAC↓, 1,   TOS↑, 1,   TrxR↓, 1,   xCT↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 2,   ATP↓, 4,   MEK↓, 2,   MMP↓, 10,   MMP↑, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

12LOX↓, 3,   ACLY↓, 1,   ACSL4↑, 1,   AKT1↓, 1,   AMPK↑, 3,   AMPK↝, 1,   ATG7↑, 1,   cMyc↓, 3,   FASN↓, 1,   GlucoseCon↓, 4,   Glycolysis↓, 5,   p‑GS3Kβ↓, 1,   H2S↑, 1,   lactateProd↓, 2,   LDH↓, 1,   LDHA↓, 2,   NADPH↑, 1,   PDH↑, 1,   PKM2↓, 4,   PPARγ↑, 1,   p‑S6↓, 1,   SIRT1↓, 1,   SREBP1↓, 1,   TCA↓, 1,  

Cell Death ⓘ

Akt↓, 33,   Akt↑, 1,   p‑Akt↓, 6,   Apoptosis↑, 26,   BAD↓, 1,   BAX↑, 13,   Bax:Bcl2↑, 4,   Bcl-2↓, 15,   Bcl-xL↓, 1,   BIM↑, 1,   Casp↑, 2,   Casp12↑, 2,   Casp3↑, 14,   Casp3∅, 1,   cl‑Casp3↑, 1,   Casp7↑, 2,   Casp8↑, 4,   Casp8∅, 1,   Casp9↑, 6,   cl‑Casp9↑, 1,   p‑Chk2↑, 1,   CK2↓, 2,   Cyt‑c↑, 13,   DR5↑, 6,   FADD↑, 1,   Fas↓, 1,   Fas↑, 5,   FasL↓, 1,   Ferroptosis↑, 4,   JNK↓, 2,   JNK↑, 2,   MAPK↓, 3,   MAPK↑, 1,   Mcl-1↓, 3,   MDM2↓, 1,   oncosis↑, 1,   p27↑, 5,   p38↑, 5,   p‑p38↓, 1,   survivin↓, 3,   Telomerase↓, 2,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,   HER2/EBBR2↓, 1,   RET↓, 1,   TSC2↑, 1,  

Transcription & Epigenetics ⓘ

other↝, 1,   tumCV↓, 4,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   eIF2α↓, 1,   ER Stress↑, 4,   GRP78/BiP↑, 1,   HSP70/HSPA5↓, 1,   HSP90↓, 3,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 3,   BNIP3↑, 1,   TumAuto↑, 6,  

DNA Damage & Repair ⓘ

p‑ATM↑, 1,   p‑ATR↑, 1,   CHK1↓, 1,   p‑CHK1↑, 1,   DNAdam↑, 6,   HR↓, 1,   p16↑, 2,   P53↓, 1,   P53↑, 6,   P53↝, 1,   p‑P53↑, 1,   cl‑PARP↑, 6,   PCNA↓, 1,   RAD51↓, 1,   SIRT6↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 2,   CDK2↓, 2,   CDK4↓, 4,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 2,   CycB/CCNB1↑, 1,   cycD1/CCND1↓, 6,   CycD3↓, 1,   cycE/CCNE↓, 2,   cycE/CCNE↑, 1,   cycE1↓, 1,   P21↑, 8,   TumCCA↑, 14,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CD44↓, 2,   cDC2↓, 1,   cMET↓, 2,   CSCs↓, 7,   EMT↓, 11,   ERK↓, 6,   p‑ERK↓, 1,   FOXO3↑, 3,   Gli↓, 1,   GSK‐3β↓, 2,   GSK‐3β↑, 1,   p‑GSK‐3β↓, 1,   HDAC↓, 2,   HDAC1↓, 1,   HDAC10↑, 1,   HDAC3↓, 1,   HH↓, 1,   IGF-1↓, 1,   IGF-1R↓, 1,   mTOR↓, 15,   p‑mTOR↓, 2,   Nanog↓, 2,   NOTCH1↓, 4,   NOTCH3↓, 2,   OCT4↓, 1,   p‑P70S6K↓, 2,   p‑P90RSK↑, 1,   PI3K↓, 37,   PI3K↑, 1,   PI3K↝, 1,   p‑PI3K↓, 3,   PTEN↑, 1,   SOX2↓, 1,   STAT↓, 1,   STAT3↓, 7,   p‑STAT3↓, 2,   TumCG↓, 8,   Wnt?, 1,   Wnt↓, 4,   Wnt/(β-catenin)↓, 3,  

Migration ⓘ

AP-1↓, 1,   AXL↓, 1,   Ca+2↑, 6,   CAFs/TAFs↓, 1,   CDK4/6↓, 1,   E-cadherin↑, 1,   FAK↓, 3,   p‑FAK↓, 1,   Furin↓, 1,   GLI2↓, 1,   ITGB1↑, 1,   Ki-67↓, 2,   miR-133a-3p↑, 1,   miR-200b↑, 1,   miR-29b↑, 2,   MMP2↓, 8,   MMP9↓, 8,   MMPs↓, 4,   N-cadherin↓, 1,   NCAM↑, 1,   Slug↓, 3,   SMAD4↓, 2,   Snail?, 1,   Snail↓, 2,   TGF-β↓, 5,   TGF-β1↓, 1,   TIMP2↑, 1,   TumCI↓, 7,   TumCMig↓, 6,   TumCP↓, 13,   TumCP↑, 1,   TumMeta↓, 8,   Twist↓, 2,   uPA↓, 3,   Vim↓, 2,   Zeb1↓, 2,   ZEB2↓, 1,   β-catenin/ZEB1↓, 5,  

Angiogenesis & Vasculature ⓘ

angioG↓, 5,   angioG↑, 1,   EGFR↓, 3,   EPR↑, 1,   HIF-1↓, 3,   Hif1a↓, 10,   KDR/FLK-1↓, 1,   NO↓, 1,   VEGF↓, 10,   VEGF↑, 1,   VEGFR2↓, 2,  

Barriers & Transport ⓘ

GLUT1↓, 4,   P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   COX2↓, 3,   CXCR4↓, 1,   IKKα↓, 1,   IL1↓, 1,   IL12↑, 1,   IL1α↓, 1,   IL2↑, 1,   IL4↓, 1,   IL6↓, 5,   IL8↓, 2,   Imm↑, 2,   Inflam↓, 2,   IκB↑, 1,   p‑IκB↓, 1,   JAK↓, 1,   M2 MC↓, 1,   MIP2↓, 1,   NF-kB↓, 15,   NF-kB↑, 2,   p50↓, 1,   PD-L1↓, 1,   PGE2↓, 2,   TNF-α↓, 3,   TNF-α↑, 1,   TNF-α∅, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 3,   ERα/ESR1↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 2,   BioAv↝, 1,   BioEnh↑, 3,   ChemoSen↑, 10,   ChemoSen⇅, 1,   Dose↝, 1,   Dose∅, 2,   eff↓, 2,   eff↑, 34,   eff↝, 3,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 4,   selectivity↑, 4,  

Clinical Biomarkers ⓘ

AR↓, 1,   E6↓, 1,   E7↓, 1,   EGFR↓, 3,   ERα/ESR1↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 5,   Ki-67↓, 2,   LDH↓, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 8,   AntiTum↑, 4,   chemoP↑, 5,   chemoPv↑, 2,   neuroP↑, 1,   OS↑, 1,   QoL↑, 2,   radioP↑, 1,   Risk↓, 2,   toxicity↓, 1,   Weight∅, 1,  
Total Targets: 297

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 11,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 5,   GSTs↑, 2,   H2O2∅, 1,   HO-1↑, 2,   Keap1↓, 1,   lipid-P↓, 1,   MDA↓, 2,   MPO↓, 1,   NRF2↑, 8,   ROS↓, 8,   SOD↑, 3,   TBARS↓, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 3,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   AMPK↑, 4,   AMPK⇅, 1,   FAO↑, 1,   glucose↓, 1,   glucose↑, 1,   GlucoseCon↑, 2,   H2S↑, 1,   LDH↓, 2,   PKM2↓, 1,   PPARγ↑, 1,   p‑PPARγ↓, 1,  

Cell Death ⓘ

Akt?, 1,   Akt↓, 2,   Akt↑, 5,   p‑Akt↑, 1,   iNOS↓, 2,   MAPK↓, 1,   MAPK↑, 3,   p38↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 1,   other↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 3,   GSK‐3β↓, 1,   PI3K↓, 3,   PI3K↑, 6,   PTEN↓, 2,  

Migration ⓘ

AntiAg↓, 1,   MMP9↓, 2,   PKCδ↑, 2,   TGF-β↓, 1,   VCAM-1↓, 3,  

Angiogenesis & Vasculature ⓘ

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

Barriers & Transport ⓘ

BBB↑, 5,   GLUT1↑, 1,   GLUT4↑, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   ICAM-1↓, 1,   IL18↓, 1,   IL1β↓, 3,   IL6?, 1,   IL6↓, 2,   IL8↓, 1,   Imm↑, 1,   Inflam↓, 9,   NF-kB↓, 5,   PGE2↓, 2,   TLR4↓, 1,   TNF-α↓, 4,  

Synaptic & Neurotransmission ⓘ

5HT↑, 1,   AChE↓, 1,   BDNF↑, 3,   GABA↑, 1,   MAOA↓, 1,   TrkB↑, 2,  

Protein Aggregation ⓘ

Aβ↓, 1,   NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↝, 3,   Dose↑, 1,   Dose↝, 1,   eff↓, 1,   eff↑, 3,   Half-Life↝, 3,   Half-Life∅, 1,  

Clinical Biomarkers ⓘ

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

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiDiabetic↑, 1,   AntiTum↑, 1,   Bone Healing↑, 1,   cardioP↑, 3,   chemoP↑, 1,   chemoPv↑, 1,   cognitive↑, 4,   hepatoP↑, 3,   memory↑, 1,   neuroP↑, 7,   toxicity↓, 2,   Wound Healing↑, 1,  

Infection & Microbiome ⓘ

AntiFungal↑, 1,   AntiViral↑, 1,   Bacteria↓, 1,  
Total Targets: 109

Scientific Paper Hit Count for: PI3K, Phosphatidylinositide-3-Kinases
18 Quercetin
16 Thymoquinone
12 Apigenin (mainly Parsley)
12 Fisetin
10 Berberine
10 Resveratrol
10 Shikonin
9 Baicalein
8 Honokiol
7 Curcumin
7 Sulforaphane (mainly Broccoli)
6 Alpha-Lipoic-Acid
6 Luteolin
6 Magnolol
6 Rosmarinic acid
6 Urolithin
5 Chrysin
5 Lycopene
5 Silymarin (Milk Thistle) silibinin
4 5-fluorouracil
4 Astragalus
4 Cisplatin
4 Propolis -bee glue
4 diet FMD Fasting Mimicking Diet
4 Ellagic acid
4 Magnetic Fields
4 Naringin
3 Silver-NanoParticles
3 Allicin (mainly Garlic)
3 Chemotherapy
3 Artemisinin
3 Astaxanthin
3 Bacopa monnieri
3 Emodin
3 Selenite (Sodium)
3 Vitamin K2
2 Coenzyme Q10
2 Auranofin
2 Ashwagandha(Withaferin A)
2 Trastuzumab
2 Baicalin
2 Biochanin A
2 Betulinic acid
2 Brucea javanica
2 brusatol
2 Boswellia (frankincense)
2 Carnosic acid
2 Capsaicin
2 Citric Acid
2 Ursolic acid
2 EGCG (Epigallocatechin Gallate)
2 Ferulic acid
2 Gambogic Acid
2 Ginseng
2 Myricetin
2 Nimbolide
2 Piperine
2 Plumbagin
2 Parthenolide
2 Pterostilbene
2 Aflavin-3,3′-digallate
1 HydroxyCitric Acid
1 Acetyl-l-carnitine
1 Andrographis
1 Aspirin -acetylsalicylic acid
1 Ascorbyl Palmitate
1 Aloe anthraquinones
1 almonertinib
1 Berbamine
1 Bufalin/Huachansu
1 borneol
1 Caffeic acid
1 Caffeic Acid Phenethyl Ester (CAPE)
1 Carvacrol
1 Dichloroacetophenone(2,2-)
1 Fucoidan
1 Gallic acid
1 Garcinol
1 Genistein (soy isoflavone)
1 Ginger/6-Shogaol/Gingerol
1 Hydrogen Gas
1 HydroxyTyrosol
1 Juglone
1 Licorice
1 Melatonin
1 Metformin
1 Magnetic Field Rotating
1 sericin
1 Phenethyl isothiocyanate
1 doxorubicin
1 Piperlongumine
1 Psoralidin
1 Radiotherapy/Radiation
1 Kaempferol
1 Paclitaxel
1 salinomycin
1 Sanguinarine
1 Formononetin
1 acetazolamide
1 Vitamin C (Ascorbic Acid)
1 Vitamin D3
1 Wogonin
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#:252  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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