Database Query Results : Apigenin (mainly Parsley), , P53

Api, Apigenin (mainly Parsley): Click to Expand ⟱
Features:

Apigenin — a plant-derived flavone (4′,5,7-trihydroxyflavone) abundant in parsley/celery/chamomile and other dietary sources, often abbreviated APG (or “Api” in some indexes). It is a small-molecule polyphenol classified as a dietary phytochemical/nutraceutical candidate with broad pleiotropic signaling effects in oncology models (cell-cycle control, apoptosis, inflammatory signaling, metabolic stress, and invasion/angiogenesis programs), but with important translation constraints driven by low aqueous solubility and extensive phase-II conjugation.

Primary mechanisms (ranked):

  1. Pleiotropic pro-apoptotic / cell-cycle checkpoint engagement (mitochondrial apoptosis, caspases; CDK/cyclin suppression; p53 context-dependent)
  2. PI3K–AKT–MAPK signaling suppression with downstream anti-proliferative and anti-migration effects
  3. Inflammation axis suppression (NF-κB; COX-2 and pro-inflammatory cytokine programs)
  4. Redox stress reprogramming (often ROS↑ in cancer models; antioxidant/NRF2 effects are context-dependent and can diverge between cancer vs normal cells)
  5. HIF-1α–glycolysis downshift with ATP stress (model-dependent)
  6. Anti-invasive / anti-EMT programs (FAK/integrins; MMP/uPA; EMT markers)
  7. Epigenetic modulation (HDAC/DNMT/EZH2 axes; context-dependent)
  8. Anti-angiogenic signaling (VEGF/related programs; model-dependent)
  9. Stemness pathway pressure (Hh/GLI, CK2; model-dependent)
  10. Chemo-/death-ligand sensitization (e.g., TRAIL sensitization reported in preclinical systems)

Bioavailability / PK relevance: Oral apigenin exposure is commonly limited by poor water solubility and extensive first-pass metabolism (glucuronidation/sulfation). Human data indicate circulating apigenin is largely present as conjugated metabolites, and dietary intake can yield only low (typically sub-µM) systemic levels; lipidic/self-emulsifying formulations can increase exposure in vivo (formulation-dependent). Reported half-life/kinetic parameters vary widely across studies and matrices.

In-vitro vs systemic exposure relevance: Many anti-cancer in vitro studies use ~10–50+ µM apigenin, which can exceed typical achievable free aglycone systemic levels after oral intake; some effects may therefore be high-concentration or formulation-enabled rather than diet-achievable. Tissue-local exposure (GI lumen, local mucosa) may be higher than plasma, and conjugate biology may contribute (context-dependent).

Clinical evidence status: Predominantly preclinical oncology evidence (cell and animal models) with limited, non-definitive human cancer interventional data; at least one pilot clinical study concept exists/has been registered (status-dependent). Strongest human evidence base is for non-cancer indications and general bioactivity rather than oncology efficacy.

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.

Apigenin — cancer-relevant mechanistic pathway matrix

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial apoptosis program ΔΨm ↓, Cyt-c ↑, Caspase cascade ↑, apoptosis ↑ ↔ to protective (model-dependent) R Pro-apoptotic stress commitment Frequently reported core phenotype across tumor models; may be downstream of ROS and kinase-network suppression.
2 Cell-cycle control Cyclin D1/E ↓, CDK2/4/6 ↓, arrest ↑ ↔ G Anti-proliferative checkpointing Often couples to p53/p21 context and growth-factor signaling downshift.
3 PI3K / AKT / MAPK PI3K ↓, AKT ↓, ERK ↓ (model-dependent) ↔ R Growth and survival signaling suppression High industry relevance; provides a convergent explanation for anti-growth and anti-migration phenotypes.
4 NF-κB / COX-2 inflammatory axis NF-κB ↓, COX-2 ↓, inflammatory cytokine programs ↓ Inflammatory tone ↓ G Anti-inflammatory microenvironment pressure Relevant to tumor-promoting inflammation and stromal signaling (context-dependent).
5 ROS modulation ROS ↑ (often), DNA damage ↑, ER stress ↑ (model-dependent) ROS injury ↓ / antioxidant support ↑ (context-dependent) P Redox stress bifurcation (tumor vs normal) Frequently described “paradox”: pro-oxidant stress in tumors while normal cells may show antioxidant protection; not universal.
6 NRF2 / antioxidant defense NRF2 ↓, GSH ↓ (often) ↔ (conflicting) NRF2 ↑, SOD ↑, GSH ↑ (context-dependent) G Antioxidant program reprogramming Direction is context- and model-dependent; important for interpreting chemo-compatibility and ROS claims.
7 HIF-1α / glycolysis HIF-1α ↓, glycolysis ↓, ATP ↓ (model-dependent) ↔ G Metabolic stress / Warburg pressure Reported suppression of glycolysis nodes (e.g., GLUT1/LDHA/HK2/PKM2/PDK1) in some models; may be concentration-sensitive.
8 Migration / invasion and EMT EMT ↓, FAK ↓, integrin signaling ↓, MMPs ↓, uPA ↓ ↔ G Anti-metastatic phenotypes Often downstream of kinase-network suppression and inflammatory tone changes.
9 Angiogenesis programs VEGF ↓ (model-dependent) ↔ G Anti-angiogenic signaling pressure Usually indirect via HIF-1α / inflammatory signaling and tumor-stromal coupling.
10 Epigenetic regulation HDAC ↓, DNMTs ↓, EZH2 ↓ (model-dependent) ↔ G Transcriptional reprogramming Mechanistically plausible but often secondary to upstream stress/kinase changes; evidence varies by model.
11 Cancer stemness pathways Hh/GLI ↓, CK2 ↓, CSC phenotypes ↓ (model-dependent) ↔ G Stemness pressure Typically preclinical; may matter for recurrence-resistance hypotheses.
12 Chemosensitization / death-ligand sensitization Sensitization ↑ (model-dependent) ↔ R Combination leverage Examples include TRAIL sensitization in vitro; translation depends on achievable exposure and interaction risk.
13 Clinical Translation Constraint Low solubility; conjugation-heavy PK; in-vitro concentration gap; potential CYP/UGT/SULT interactions Drug–supplement interaction risk relevant to both — Delivery and interaction limitations Oral free-aglycone systemic levels are often low; formulation can change exposure. In vitro CYP inhibition is reported (notably CYP3A4/2C9); apigenin can also inhibit conjugation pathways in models—caution with narrow-therapeutic-index drugs.

TSF

P: 0–30 min
R: 30 min–3 hr
G: >3 hr
P53, P53-Guardian of the Genome: Click to Expand ⟱
Source: TCGA
Type: Proapototic
TP53 is the most commonly mutated gene in human cancer. TP53 is a gene that encodes for the p53 tumor suppressor protein ; TP73 (Chr.1p36.33) and TP63 (Chr.3q28) genes that encode transcription factors p73 and p63, respectively, are TP53 homologous structures.
p53 is a crucial tumor suppressor protein that plays a significant role in regulating the cell cycle, maintaining genomic stability, and preventing tumor formation. It is often referred to as the "guardian of the genome" due to its role in protecting cells from DNA damage and stress.
TP53 gene, which encodes the p53 protein, is one of the most frequently mutated genes in human cancers.
Overexpression of MDM2, an inhibitor of p53, can lead to decreased p53 activity even in the presence of wild-type p53.
In some cancers, particularly those with mutant p53, there may be an overexpression of the p53 protein.
Cancers with overexpression: Breast, lung, colorectal, overian, head and neck, Esophageal, bladder, pancreatic, and liver.
Scientific Papers found: Click to Expand⟱
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%

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

1553- Api,    Role of Apigenin in Cancer Prevention via the Induction of Apoptosis and Autophagy
- Review, NA, NA
Dose∅, oral administration of apigenin (20 and 50 μg/mice) for 20 weeks reduced tumor volumes
TumVol↓,
Dose∅, 15-week period of oral administration of apigenin (2.5 mg/kg) in hamsters resulted in reduction of tumor volume
COX2↓, topical application of apigenin (5 μM) prior to UVB-exposure attenuated the expression of COX-2 and hypoxia inducible factor (HIF)-1α,
Hif1a↓,
TumCCA↑, apigenin was capable to promote cell cycle arrest and induction of apoptosis through p53-related pathways
P53↑,
P21↑, induction of the cell cycle inhibitor p21/WAF1,
Casp3↑,
DNAdam↑, DNA fragmentation
TumAuto↝, Only a small number of studies have observed the induction of autophagy in response to apigenin and the results are controversial

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↓,

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)↓,

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

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↓,

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

310- Api,    Apigenin inhibits renal cell carcinoma cell proliferation
- vitro+vivo, RCC, ACHN - in-vitro, RCC, 786-O - in-vitro, RCC, Caki-1 - in-vitro, RCC, HK-2
TumCCA↑, G2/M cell cycle arrest.
p‑ATM↑, p-ATM
p‑CHK1↑, p-Chk2
p‑CDC25↑, p-Cdc25c
p‑cDC2↑, phosphorylated Cdc2 (p-Cdc2 on tyrosine15), also increased
P53↑, 10, 20, 40 uM
BAX↑,
Casp9↑,
Casp3↑,

180- Api,    Induction of caspase-dependent apoptosis by apigenin by inhibiting STAT3 signaling in HER2-overexpressing MDA-MB-453 breast cancer cells
- in-vitro, BC, MDA-MB-231
cl‑Casp8↑, cleaved
cl‑Casp3↑, cleaved
cl‑PARP↑, cleaved
BAX∅, failed to regulate
Bcl-2∅, failed to regulate
Bcl-xL∅, failed to regulate
p‑STAT3↓,
P53↑,
P21↑,
p‑JAK2↓, p-JAK2
VEGF↓,

176- Api,    Induction of caspase-dependent extrinsic apoptosis by apigenin through inhibition of signal transducer and activator of transcription 3 (STAT3) signalling in HER2-overexpressing BT-474 breast cancer cells
- in-vitro, BC, BT474
cl‑Casp8↑, apigenin up-regulated the levels of cleaved caspase-8 and caspase-3, and induced the cleavage of PARP in BT-474 cells
cl‑Casp3↑,
p‑JAK1↓, apigenin reduced the expression of p-STAT3 as well as p-JAK1 and p-JAK2 (upstream kinases of STAT3)
p‑JAK2↓,
p‑STAT3↓,
P53↑,
VEGF↓, pigenin also reduced the level of VEGF
Hif1a↓, apigenin suppressed the expression of p-STAT3 and HIF-1α that was up-regulated by CoCl2 (hypoxia mimic)
MMP9↓,
TumCG↓, Apigenin suppresses the growth of BT-474 cells
TumCCA↑, The growth-suppressive activity of apigenin is accompanied by an increase in the sub-G 0 /G 1 apoptotic population in BT-474 cells
cl‑PARP↑,

173- Api,    Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells
- in-vitro, Colon, HCT116
CycB/CCNB1↓,
cDC2↓,
CDC25↓,
P53↑,
P21↑,
cl‑PARP↑, cleavage
proCasp8↓, Apigenin induced poly (ADP-ribose) polymerase (PARP) cleavage and decreased the levels of procaspase-8, -9 and -3
proCasp9↓,
proCasp3↓,

581- Api,  Cisplatin,    The natural flavonoid apigenin sensitizes human CD44+ prostate cancer stem cells to cisplatin therapy
- in-vitro, Pca, CD44+
Bcl-2↓,
survivin↓,
Casp8↑,
P53↑,
Sharpin↓,
APAF1↑,
p‑Akt↓,
NF-kB↓,
P21↑,
Cyc↓,
CDK2↓,
CDK4/6↓,
Snail↓,
ChemoSen↑, Apigenin significantly increased the inhibitory effects of cisplatin on cell migration via downregulation of Snail expression

578- Api,  Cisplatin,    Apigenin enhances the cisplatin cytotoxic effect through p53-modulated apoptosis
- in-vitro, Lung, A549 - in-vitro, BC, MCF-7 - in-vitro, CRC, HCT116 - in-vitro, Pca, HeLa - in-vitro, Lung, H1299
p‑P53↑,

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


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   GSH↓, 1,   ROS↓, 1,   ROS↑, 5,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   CDC25↓, 1,   p‑CDC25↑, 1,   MMP↓, 3,  

Core Metabolism/Glycolysis ⓘ

FASN↓, 1,   GlucoseCon↓, 1,   PKM2↓, 1,   p‑S6↓, 1,  

Cell Death ⓘ

Akt↓, 3,   p‑Akt↓, 3,   APAF1↑, 2,   Apoptosis↑, 4,   Bak↑, 1,   BAX↑, 5,   BAX∅, 1,   Bax:Bcl2↑, 3,   Bcl-2↓, 6,   Bcl-2∅, 1,   Bcl-xL↓, 3,   Bcl-xL∅, 1,   BIM↑, 1,   Casp↑, 3,   Casp3↑, 5,   cl‑Casp3↑, 3,   proCasp3↓, 1,   cl‑Casp7↑, 1,   Casp8↑, 3,   cl‑Casp8↑, 3,   proCasp8↓, 1,   Casp9↑, 4,   cl‑Casp9↑, 1,   proCasp9↓, 1,   CK2↓, 2,   Cyt‑c↑, 5,   cl‑IAP2↑, 1,   p‑JNK↓, 2,   MDM2↓, 1,   MLKL↑, 1,   p‑MLKL↓, 1,   Necroptosis↑, 1,   p‑p38↑, 1,   survivin↓, 1,   Telomerase↓, 1,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   p‑pRB↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 1,   HSPs↓, 1,  

Autophagy & Lysosomes ⓘ

LC3B↑, 1,   p62↑, 1,   TumAuto↑, 2,   TumAuto↝, 1,  

DNA Damage & Repair ⓘ

p‑ATM↑, 1,   p‑CHK1↑, 1,   DNAdam↑, 3,   P53↓, 1,   P53↑, 12,   p‑P53↑, 2,   p‑PARP↑, 1,   cl‑PARP↑, 5,   cl‑PARP1↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 2,   CDK2↓, 1,   CDK4↓, 1,   Cyc↓, 1,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 2,   P21↑, 8,   TumCCA↑, 8,  

Proliferation, Differentiation & Cell State ⓘ

cDC2↓, 1,   p‑cDC2↑, 1,   EMT↓, 1,   ERK↓, 2,   p‑ERK↓, 1,   p‑ERK⇅, 1,   p‑GSK‐3β↓, 1,   IGF-1↓, 1,   IGFBP3↑, 1,   mTOR↓, 2,   p‑P70S6K↓, 1,   p‑P90RSK↑, 1,   PI3K↓, 2,   STAT3↓, 3,   p‑STAT3↓, 2,   TumCG↓, 2,   TumCG↑, 1,   Wnt/(β-catenin)↓, 2,  

Migration ⓘ

AntiAg↑, 1,   Ca+2↑, 2,   cal2↑, 1,   CDK4/6↓, 1,   E-cadherin↑, 1,   FAK↓, 1,   ITGB4↓, 1,   MMP2↓, 1,   MMP9↓, 2,   MMPs↓, 1,   RIP3↑, 1,   p‑RIP3↑, 1,   Sharpin↓, 1,   Snail↓, 1,   TumCI↓, 4,   TumCMig↓, 3,   TumCP↓, 2,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

ATF4↑, 1,   EGFR↓, 2,   Hif1a↓, 5,   VEGF↓, 5,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IKKα↓, 1,   IL1α↓, 1,   IL6↓, 1,   p‑JAK1↓, 1,   p‑JAK2↓, 2,   NF-kB↓, 3,   p65↓, 1,   PSA↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   Dose∅, 4,   eff↓, 2,   eff↑, 4,   selectivity↓, 1,   selectivity↑, 3,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 2,   HER2/EBBR2↓, 1,   IL6↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,   TumVol↓, 2,   TumW↓, 2,  
Total Targets: 143

Pathway results for Effect on Normal Cells:


Cell Death ⓘ

MAPK↓, 1,  

Migration ⓘ

PKCδ↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   Half-Life∅, 1,  

Functional Outcomes ⓘ

toxicity↓, 1,  
Total Targets: 6

Scientific Paper Hit Count for: P53, P53-Guardian of the Genome
15 Apigenin (mainly Parsley)
2 Cisplatin
1 Metformin
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#:32  Target#:236  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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