condition found tbRes List
Api, Apigenin (mainly Parsley): Click to Expand ⟱
Features:
Apigenin present in parsley, celery, chamomile, oranges and beverages such as tea, beer and wine.
"It exhibits cell growth arrest and apoptosis in different types of tumors such as breast, lung, liver, skin, blood, colon, prostate, pancreatic, cervical, oral, and stomach, by modulating several signaling pathways."
-Note half-life reports vary 2.5-90hrs?.
-low solubility of apigenin in water : BioAv (improves when mixed with oil/dietary fat or lipid based formulations)
-best oil might be MCT oils (medium-chain fatty acids)


Pathways:
- Often considered an antioxidant, in cancer cells it can paradoxically induce ROS production
(one report that goes against most others, by lowering ROS in cancer cells but still effective)
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, UPR↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, GSH↓ (Conflicting evidence about Nrf2)
        - Combined with Metformin (reduces Nrf2) amplifies ROS production in cancer cells while sparing normal cells.
- Raises AntiOxidant defense in Normal Cells: NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : , MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, PDK1↓, GLUT1↓, LDHA↓, HK2↓, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, GLi↓, GLi1↓,
- Others: PI3K↓, AKT↓, JAK↓, 1, 2, 3, STAT↓, 1, 2, 3, 4, 5, 6, Wnt↓, β-catenin↓, AMPK↓,, α↓,, ERK↓, 5↓, JNK↓,
- Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes)
        -Ex: other flavonoids(chrysin, Luteolin, querectin) curcumin, metformin, sulforaphane, ASA
Neuroprotective, Renoprotection, Hepatoprotective, CardioProtective,
- Selectivity: Cancer Cells vs Normal Cells

Apigenin exhibits biological effects (anticancer, anti-inflammatory, antioxidant, neuroprotective, etc.) typically at concentrations roughly in the range of 1–50 µM.

Parsley microgreens can contain up to 2-3 times more apigenin than mature parsley.
Apigenin is typically measured in the range of 1-10 μM for biological activity. Assuming a molecular weight of 270 g/mol for apigenin, we can estimate the following μM concentrations:
10uM*5L(blood)*270g/mol=13.5mg apigenin (assumes 100% bioavailability)
then an estimated 10-20 mg of apigenin per 100 g of fresh weight parlsey
2.2mg/g of apigenin fresh parsley
45mg/g of apigenin in dried parsley (wikipedia)
so 100g of parsley might acheive 10uM blood serum level (100% bioavailability)
BUT bioavailability is only 1-5%
(Supplements available in 75mg liposomal)( Apigenin Pro Liposomal, 200 mg from mcsformulas.com)

A study had 2g/kg bw (meaning 160g for 80kg person) delivered a maximum 0.13uM of plasma concentration @ 7.2hrs.
Assuming parsley is 90-95% water, then that would be ~16g of dried parsley
Conclusion: to reach 10uM would seem very difficult by oral ingestion of parsley.
Other quotes:
      “4g of dried parsley will be enough for 50kg adult”
      5mg/kg BW yields 16uM, so 80Kg person means 400mg (if dried parsley is 130mg/g, then would need 3g/d)
In many cancer cell lines, concentrations in the range of approximately 20–40 µM have been reported to shift apigenin’s activity from mild antioxidant effects (or negligible ROS changes) toward a clear pro-oxidant effect with measurable ROS increases.

Low doses: At lower concentrations, apigenin is more likely to exhibit its antioxidant properties, scavenging ROS and protecting cells from oxidative stress.
In normal cells with robust antioxidant systems, apigenin’s antioxidant effects might prevail, whereas cancer cells—often characterized by an already high level of basal ROS—can be pushed over the oxidative threshold by increased ROS production induced by apigenin.
In environments with lower free copper levels, this pro-oxidant activity is less pronounced, and apigenin may tilt the balance toward its antioxidant function.
ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK: regulates energy metabolism and can increase ROS levels when activated.
• mTOR: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Melavonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day
-Dipyridamole typically 200mg 2x/day
-Lycopene typically 100mg/day range

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

Scientific Papers found: Click to Expand⟱
1563- Api,  MET,    Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells
- in-vitro, Nor, HDFa - in-vitro, PC, AsPC-1 - in-vitro, PC, MIA PaCa-2 - in-vitro, Pca, DU145 - in-vitro, Pca, LNCaP - in-vivo, NA, NA
selectivity↑, Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts.
selectivity↑, Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells
selectivity↓, Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells
ROS↑,
eff↑, Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect.
tumCV↓,
MMP↓, Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells
Dose∅, co-treatment with metformin (0.05, 0.5 or 5 mM) and apigenin (20 µM) dramatically increased cellular ROS levels in AsPC-1 cells
eff↓, NAC blocked the metformin/apigenin co-treatment-induced cell death in AsPC-1 cells
DNAdam↑, Combination of metformin and apigenin leads to DNA damage-induced apoptosis, autophagy and necroptosis in AsPC-1 cells but not in HDF cells
Apoptosis↑,
TumAuto↑,
Necroptosis↑,
p‑P53↑, p-p53, Bim, Bid, Bax, cleaved PARP, caspase 3, caspase 8, and caspase 9 were also significantly increased by combination of metformin and apigenin in AsPC-1
BIM↑,
BAX↑,
p‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑, Cytochrome C was also released from mitochondria in AsPC-1 cell
Bcl-2↓,
AIF↑, Interestingly, autophagy-related proteins (AIF, P62 and LC3B) and necroptosis-related proteins (MLKL, p-MLKL, RIP3 and p-RIP3) were also increased by combination of metformin and apigenin
p62↑,
LC3B↑,
MLKL↑,
p‑MLKL↓,
RIP3↑,
p‑RIP3↑,
TumCG↑, in vivo
TumW↓, metformin (125 mg/kg) or apigenin (40 mg/kg) caused a reduction of tumor size compared to the control group (Fig. 7D). However, oral administration of combination of metformin and apigenin decreased tumor weight profoundly

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↓,

1537- Api,    Apigenin as Tumor Suppressor in Cancers: Biotherapeutic Activity, Nanodelivery, and Mechanisms With Emphasis on Pancreatic Cancer
- Review, PC, NA
TumCP↓,
TumCCA↑,
Apoptosis↑,
MMPs↓,
Akt↓,
*BioAv↑, delivery systems (nanosuspension, polymeric micelles, liposomes).
*BioAv↓, low solubility of apigenin in water (1.35 μg/mL) and its high permeability
Half-Life∅, (appearing in blood circulation after 3.9 h)
Hif1a↓, (HIF-1α) is targeted by apigenin in several cancers such as, ovarian cancer, prostate cancer, and lung cancer
GLUT1↓, GLUT-1 is blocked by apigenin (0–100 μM) under normoxic conditions
VEGF↓,
ChemoSen↑, apigenin can be applied as a chemosensitizer
ROS↑, accumulation of ROS produced were stimulated
Bcl-2↓, down-regulation of anti-apoptotic factors Bcl-2 and Bcl-xl as well as the up-regulation of apoptotic factors Bax and Bim.
Bcl-xL↓,
BAX↑,
BIM↑,

1536- Api,    Apigenin causes necroptosis by inducing ROS accumulation, mitochondrial dysfunction, and ATP depletion in malignant mesothelioma cells
- in-vitro, MM, MSTO-211H - in-vitro, MM, H2452
tumCV↓,
ROS↑, increase in intracellular reactive oxygen species (ROS)
MMP↓, caused the loss of mitochondrial membrane potential (ΔΨm)
ATP↓, ATP depletion
Apoptosis↑,
Necroptosis↑,
DNAdam↑,
TumCCA↑, delay at the G2/M phase of cell cycle
Casp3↑,
cl‑PARP↑,
MLKL↑,
p‑RIP3↑,
Bax:Bcl2↑,
eff↓, ATP supplementation restored cell viability and levels of DNA damage-, apoptosis- and necroptosis-related proteins that apigenin caused.
eff↓, N-acetylcysteine reduced ROS production and improved ΔΨm loss and cell death that were caused by apigenin.

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

2640- Api,    Apigenin: A Promising Molecule for Cancer Prevention
- Review, Var, NA
chemoP↑, 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↑,

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.
chemoP↑, 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↓, 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).

2638- Api,    Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death
- in-vitro, lymphoma, PEL
TumCD↑, We show that apigenin induced PEL cell death and autophagy along with reduction of intracellular ROS.
TumAuto↑,
ROS↓,
P53↑, Mechanistically, apigenin activated p53 that induced catalase, a ROS scavenger enzyme, and inhibited STAT3, the most important pro-survival pathway in PEL, as assessed by p53 silencing.
Catalase↑,
STAT3↓,

2637- Api,    Apigenin Alleviates Endoplasmic Reticulum Stress-Mediated Apoptosis in INS-1 β-Cells
- in-vitro, Diabetic, NA
*other↝, In the present study, the anti-diabetic effect of apigenin on pancreatic β-cell insulin secretion, apoptosis, and the mechanism underlying its anti-diabetic effects, were investigated in the INS-ID β-cell line
*Insulin↑, The results showed that apigenin concentration-dependently facilitated 11.1-mM glucose-induced insulin secretion, which peaked at 30 µM
ER Stress↓, Apigenin also concentration-dependently inhibited the expression of endoplasmic reticulum (ER) stress signaling proteins
*CHOP↓, CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) and cleaved caspase-3
*cl‑Casp3↓,
*ROS↓, In contrast, the cytoprotective effect of apigenin against oxidative stress, inflammation, apoptosis, and oxidative and ER stresses has been demonstrated in various cell types
*Inflam↓,
*TXNIP↓, expression of TXNIP, which was increased by the thapsigargin treatment, was downregulated in INS-1D cells in response to apigenin.

2634- Api,    Apigenin induces both intrinsic and extrinsic pathways of apoptosis in human colon carcinoma HCT-116 cells
- in-vitro, CRC, HCT116
TumCG↓, Apigenin exerted cytotoxic effect on the cells via inhibiting cell growth in a dose-time-dependent manner and causing morphological changes, arrested cell cycle progression at G0/G1 phase
TumCCA↑,
MMP↓, decreased mitochondrial membrane potential of the treated cells
ROS↑, Apigenin increased respective ROS generation and Ca2+ release and thereby, caused ER stress in the treated cells.
Ca+2↑,
ER Stress↑,
mtDam↑, together with damaged mitochondrial membrane, and upregulated protein expression of CHOP, DR5, cleaved BID, Bax, cytochrome c, cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, which triggered apoptosis of the cells.
CHOP↑,
DR5↑,
cl‑BID↑,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
Apoptosis↑,

2633- Api,    Apigenin induces ROS-dependent apoptosis and ER stress in human endometriosis cells
- in-vitro, EC, NA
TumCP↓, Apigenin reduced proliferation and induced cell cycle arrest and apoptosis in the both endometriosis cell lines
TumCCA↑,
MMP↓, In addition, it disrupted mitochondrial membrane potential (MMP) which was accompanied by an increase in concentration of calcium ions in the cytosol and in pro-apoptotic proteins including Bax and cytochrome c in the VK2/E6E7 and End1/E6E7 cells
Ca+2↑,
BAX↑,
Cyt‑c↑,
ROS↑, Moreover, apigenin treated cells accumulated excessive reactive oxygen species (ROS), and experienced lipid peroxidation and endoplasmic reticulum (ER) stress with activation of the unfolded protein response (UPR) regulatory proteins.
lipid-P↑,
ER Stress↑,
UPR↑,
p‑ERK↓, Apigenin inhibited the phosphorylation of ERK1/2
ERK↓, Similar to previous studies, apigenin-induced apoptosis was also mediated by inactivation of ERK1/2 and JNK proteins and regulation of AKT protein in human endometriosis cells.
JNK↑,

2632- Api,    Apigenin inhibits migration and induces apoptosis of human endometrial carcinoma Ishikawa cells via PI3K-AKT-GSK-3β pathway and endoplasmic reticulum stress
- in-vitro, EC, NA
TumCP↓, We found that API could inhibit the proliferation of Ishikawa cells at IC50 of 45.55 μM, arrest the cell cycle at G2/M phase, induce apoptosis by inhibiting Bcl-xl and increasing Bax, Bak and Caspases.
TumCCA↑,
Apoptosis↑,
Bcl-2↓,
BAX↑,
Bak↑,
Casp↑,
ER Stress↑, Further, API could induce apoptosis by activating the endoplasmic reticulum (ER) stress pathway by increasing the Ca2+, ATF4, and CHOP.
Ca+2↑, after API treatment for 48 h, the intracellular Ca2+ concentration increased in cells in a dose-dependent manner.
ATF4↑,
CHOP↑,
ROS↑, the level of intracellular ROS increased gradually with the increase of API concentration.
MMP↓, mitochondrial membrane potential of 30 μM, 50 μM, and 70 μM groups decreased by 2.19%, 11.32%, and 14.91%, respectively.
TumCMig↓, API inhibits the migration and invasion of Ishikawa cells and the migration and invasion related gene and protein.
TumCI↓,
eff↑, In our study, API restrained the viability of Ishikawa cells, and the inhibition effect of API on Ishikawa cells was better than that of 5-FU.
P53↑, API induces p53 tumor suppressor proteins at the translational level and the induces p21
P21↑,
Cyt‑c↑, After the mitochondria release the Cyto-c, the Caspase-9 is activated, resulting in increased activity of Caspases
Casp9↑, In our study, the expression levels of Bad, Bax, Cyto-c, Caspase-9 and Caspase-3 proteins were up-regulated,
Casp3↑,
Bcl-xL↓, while the expression level of Bcl-xl was down-regulated

2631- Api,    Apigenin Induces Autophagy and Cell Death by Targeting EZH2 under Hypoxia Conditions in Gastric Cancer Cells
- in-vivo, GC, NA - in-vitro, GC, AGS
ER Stress↑, We further show that APG induces ER stress- and autophagy-related cell death through the inhibition of HIF-1α and Ezh2 under normoxia and hypoxia.
Hif1a↓, APG Inhibits HIF-1α and Induces Cell Death under Hypoxia in GC Cells
EZH2↓,
HDAC↓, Apigenin, a flavonoid found in traditional medicine, fruits, and vegetables and an HDAC inhibitor, is a powerful anti-cancer agent against various cancer cell lines.
TumAuto↑, APG Induces Autophagic Cell Death in GC Cells
p‑mTOR↓, APG decreased the phosphorylation of mTOR and increased the activation of AMPKα and ULK1
AMPKα↑,
GRP78/BiP↑, APG mediates the up-regulation of GRP78 through exosomes, and that this effect causes ER stress-induced cell death in APG-treated GC cells.
ROS↑, APG generates intracellular ROS release in colorectal cancer cells, and it causes various cell death types, including cell cycle arrest, chromatin condensation, MMP loss, intracellular Ca2+, annexin-v-positive cells, and ER stress-related cell death
MMP↓,
Ca+2↑, we found that APG exerts intracellular Ca2+ release in a dose- and time-dependent manner
ATF4↑, APG also increased ATF4 and CHOP in a time-dependent manner
CHOP↑,

2583- Api,  Rad,    The influence of apigenin on cellular responses to radiation: From protection to sensitization
- Review, Var, NA
radioP↑, apigenin's radioprotective and radiosensitive properties
RadioS↑,
*COX2↓, When exposed to irradiation, apigenin reduces inflammation via cyclooxygenase-2 inhibition and modulates proapoptotic and antiapoptotic biomarkers.
*ROS↓, Apigenin's radical scavenging abilities and antioxidant enhancement mitigate oxidative DNA damage
VEGF↓, It inhibits radiation-induced mammalian target of rapamycin activation, vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP), and STAT3 expression,
MMP2↓,
STAT3↓,
AMPK↑, while promoting AMPK, autophagy, and apoptosis, suggesting potential in cancer prevention.
Apoptosis↑,
MMP9↓, radiosensitizer, apigenin inhibits tumor growth by inducing apoptosis, suppressing VEGF-C, tumor necrosis factor alpha, and STAT3, reducing MMP-2/9 activity, and inhibiting cancer cell glucose uptake.
glucose↓,

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.

2317- Api,    Apigenin intervenes in liver fibrosis by regulating PKM2-HIF-1α mediated oxidative stress
- in-vivo, Nor, NA
*hepatoP↑, promoting the recovery of liver function in mice with liver fibrosis.
*PKM2↓, API inhibits the transition of Pyruvate kinase isozyme type M2 (PKM2) from dimer to tetramer
*Hif1a↓, blocking PKM2-HIF-1α access
*MDA↓, leads to a decrease in malondialdehyde (MDA) and Catalase (CAT) levels and an increase in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) levels, as well as total antioxidant capacity (T-AOC) in the liver of mice
*Catalase↓,
*GSH↑,
*SOD↑,
*GPx↑,
*TAC↑,
*α-SMA↓, API downregulated the expression of α-smooth muscle actin (α-SMA), Vimentin and Desmin in the liver tissue of mice with liver fibrosis
*Vim↓,
*ROS↓, API can inhibit HSC activation and alleviate CCl4 induced liver fibrosis by inhibiting the PKM2-HIF-1α pathway and reducing oxidative stress,

1999- Api,  doxoR,    Apigenin ameliorates doxorubicin-induced renal injury via inhibition of oxidative stress and inflammation
- in-vitro, Nor, NRK52E - in-vitro, Nor, MPC5 - in-vitro, BC, 4T1 - in-vivo, NA, NA
neuroP↑, APG has a protective role against DOX-induced nephrotoxicity
ChemoSen∅, without weakening DOX cytotoxicity in malignant tumors.
RenoP↑, potential protective agent against renal injury. attenuate renal toxicity in cancer patients treated with DOX.
selectivity↑, APG maintained the cytotoxicity of DOX to tumor cells but not to renal cells. APG alone exhibited a prominent cytotoxic effect on 4T1 cells (Fig. 9E), but not on normal renal cells, at the same concentration
chemoP↑, Furthermore, APG revealed a dose-dependent improvement in normal renal cells against DOX-induced injury (Fig. 9E), with an exacerbation observed in 4T1 cells
ROS↑, Our in vivo study revealed that DOX caused a severe reduction in SOD activity and GSH levels, accompanied by an increase in MDA, leading to the overproduction of ROS and induction of oxidative injuries.
*ROS∅, Noteworthily, these changes were suppressed by APG(meaning on normal cells), consistent with several previous reports
*antiOx↑, APG has a similar antioxidative role as NAC and scavenges DOX-induced oxygen radicals and inhibits apoptosis significantly, implying that antioxidative stress is one of the main mechanisms through which APG protects renal tubular cells against DOX cy
*toxicity↓, We confirmed that APG mitigated the toxicity of DOX on normal renal cells by inhibiting oxidative stress, inflammation, and apoptosis.

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↓,

1564- Api,    Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation
- in-vitro, Pca, 22Rv1 - in-vivo, NA, NA
MDM2↓, downregulation of MDM2 protein
NF-kB↓, Exposure of 22Rv1 cells to 20 μM apigenin caused a decrease in NF-κB/p65 transcriptional activity by 24% at 12 h, which was further decreased to 41% at 24 h
p65↓,
P21↑,
ROS↑, Apigenin at these doses resulted in ROS generation
GSH↓, which was accompanied by rapid glutathione depletion
MMP↓, disruption of mitochondrial membrane potential
Cyt‑c↑, cytosolic release of cytochrome c
Apoptosis↑,
P53↑, accumulation of a p53 fraction to the mitochondria, which was rapid and occurred between 1 and 3 h after apigenin treatment
eff↓, All these effects were significantly blocked by pretreatment of cells with the antioxidant N-acetylcysteine
Bcl-xL↓,
Bcl-2↓,
BAX↑,
Casp↑, triggering caspase activation
TumCG↓, in vivo mice
TumVol↓, tumor volume was inhibited by 44 and 59%
TumW↓, wet weight of tumor was decreased by 41 and 53%

171- Api,    Apigenin in cancer therapy: anti-cancer effects and mechanisms of action
- Review, Var, NA
PI3K/Akt↓,
NF-kB↓,
CK2↓,
FOXO↓,
MAPK↝, modulation of MAPKs by apigenin contributed to apigenin-induced cell cycle arrest at G0/G1 phase
ERK↓, p-ERK1/2,
p‑JAK↓, phosphorylation
Wnt/(β-catenin)↓,
ROS↑, accumulation of reactive oxygen species (ROS) production, leading to induction of DNA damage
CDC25↓,
p‑STAT↓,
DNAdam↑,

586- Api,  5-FU,    5-Fluorouracil combined with apigenin enhances anticancer activity through mitochondrial membrane potential (ΔΨm)-mediated apoptosis in hepatocellular carcinoma
- in-vivo, HCC, NA
ROS↑,
MMP↓,
Bcl-2↓,
Casp3↑,
PARP↑,

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

313- Api,    Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells
- in-vitro, Thyroid, BCPAP
LC3s↝, conversion of LC3 protein
p62↓,
ROS↑,
TumCCA↑, G2/M cell cycle arrest.
CDC25↓,
TumAuto↑,
Beclin-1↑,
AVOs↑,
DNAdam↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 23

Results for Effect on Cancer/Diseased Cells:
AIF↑,1,   Akt↓,6,   p‑Akt↓,1,   AMPK↑,1,   AMPKα↑,1,   angioG↓,2,   AntiAg↑,1,   AntiCan↑,1,   AntiTum↑,1,   APAF1↑,1,   Apoptosis↑,9,   AR↓,1,   ATF4↑,2,   ATP↓,1,   AVOs↑,1,   Bak↑,1,   BAX↑,6,   Bax:Bcl2↑,5,   Bcl-2↓,6,   Bcl-xL↓,3,   Beclin-1↑,1,   cl‑BID↑,1,   BIM↑,2,   BioEnh↑,1,   Ca+2↑,6,   cal2↑,1,   Casp↑,3,   Casp12↑,1,   Casp3↑,5,   cl‑Casp3↑,2,   cl‑Casp7↑,1,   Casp8↑,2,   cl‑Casp8↑,2,   Casp9↑,4,   cl‑Casp9↑,2,   Catalase↓,1,   Catalase↑,1,   CDC25↓,2,   CDK1↓,1,   CDK2↓,1,   CDK4↓,2,   CDK6↓,1,   chemoP↑,3,   ChemoSen↑,3,   ChemoSen∅,1,   CHOP↑,3,   cJun↓,1,   CK2↓,5,   cMyc↓,1,   COX2↓,2,   CSCs↓,2,   cycD1↓,1,   CycD3↓,1,   Cyt‑c↑,10,   DNAdam↑,4,   Dose∅,2,   DR5↑,1,   E-cadherin↑,2,   eff↓,4,   eff↑,11,   eff↝,1,   EGFR↓,2,   EMT↓,2,   ER Stress↓,1,   ER Stress↑,4,   ERK↓,3,   p‑ERK↓,1,   p‑ERK⇅,1,   EZH2↓,1,   FAK↓,3,   FASN↓,1,   FOXO↓,1,   FOXO3↑,2,   Gli↓,1,   glucose↓,1,   GLUT1↓,2,   GRP78/BiP↑,1,   GSH↓,3,   p‑GSK‐3β↓,2,   Half-Life∅,1,   HDAC↓,3,   HDAC1↓,1,   HDAC3↓,1,   HER2/EBBR2↓,2,   Hif1a↓,5,   HSP90↓,1,   HSPs↓,1,   cl‑IAP2↑,1,   IGF-1↓,2,   IGFBP3↑,1,   IL6↓,1,   IL8↓,1,   ITGB4↓,1,   p‑JAK↓,1,   JNK↑,1,   p‑JNK↓,2,   LC3B↑,1,   LC3s↝,1,   lipid-P↑,1,   MAPK↝,1,   MDA↑,1,   MDM2↓,1,   MLKL↑,2,   p‑MLKL↓,1,   MMP↓,10,   MMP↑,1,   MMP2↓,3,   MMP9↓,3,   MMPs↓,3,   mtDam↑,1,   mTOR↓,1,   p‑mTOR↓,1,   NADPH↑,1,   Nanog↓,1,   Necroptosis↑,2,   neuroP↑,1,   NF-kB↓,5,   NRF2↓,3,   OCT4↓,1,   OS↑,1,   P21↑,3,   p27↑,1,   p38↑,1,   p‑p38↑,1,   P53↓,1,   P53↑,4,   p‑P53↑,1,   p62↓,1,   p62↑,1,   p65↓,1,   PARP↑,1,   p‑PARP↑,1,   cl‑PARP↑,3,   cl‑PARP1↑,1,   PI3K↓,4,   p‑PI3K↓,1,   PI3K/Akt↓,1,   p‑pRB↓,1,   PSA↓,1,   radioP↑,1,   RadioS↑,1,   RenoP↑,1,   RIP3↑,1,   p‑RIP3↑,2,   ROS↓,1,   ROS↑,18,   selectivity↓,1,   selectivity↑,3,   SIRT3↓,1,   SIRT6↓,1,   SOD↓,1,   p‑STAT↓,1,   STAT3↓,4,   p‑STAT3↓,1,   survivin↓,1,   Telomerase↓,3,   TumAuto↑,4,   TumCCA↑,9,   TumCD↑,1,   TumCG↓,2,   TumCG↑,1,   TumCI↓,4,   TumCMig↓,3,   TumCP↓,5,   tumCV↓,2,   TumMeta↓,1,   TumVol↓,1,   TumW↓,2,   Twist↓,1,   uPA↓,1,   UPR↑,1,   VEGF↓,4,   Wnt/(β-catenin)↓,1,   XIAP↓,1,   β-catenin/ZEB1↓,2,  
Total Targets: 175

Results for Effect on Normal Cells:
Akt↑,1,   AMPK↑,1,   antiOx↑,2,   BioAv↓,1,   BioAv↑,1,   cl‑Casp3↓,1,   Catalase↓,1,   CHOP↓,1,   COX2↓,1,   GPx↑,1,   GSH↑,1,   hepatoP↑,1,   Hif1a↓,2,   Inflam↓,4,   Insulin↑,1,   MAPK↓,1,   MDA↓,1,   NF-kB↓,1,   NRF2↑,1,   other↝,1,   PI3K↓,1,   PKCδ↓,1,   PKM2↓,2,   ROS↓,4,   ROS∅,1,   SOD↑,1,   TAC↑,1,   TGF-β↓,1,   toxicity↓,1,   TXNIP↓,1,   Vim↓,1,   α-SMA↓,1,  
Total Targets: 32

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
23 Apigenin (mainly Parsley)
1 Metformin
1 Radiotherapy/Radiation
1 doxorubicin
1 5-fluorouracil
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:32  Target#:275  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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