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.
Hif1a, HIF1α/HIF1a: Click to Expand ⟱
Source:
Type:
Hypoxia-Inducible-Factor 1A (HIF1A gene, HIF1α, HIF-1α protein product)
-Dominantly expressed under hypoxia(low oxygen levels) in solid tumor cells
-HIF1A induces the expression of vascular endothelial growth factor (VEGF)
-High HIF-1α expression is associated with Poor prognosis
-Low HIF-1α expression is associated with Better prognosis

-Functionally, HIF-1α is reported to regulate glycolysis, whilst HIF-2α regulates genes associated with lipoprotein metabolism.
-Cancer cells produce HIF in response to hypoxia in order to generate more VEGF that promote angiogenesis

Key mediators of aerobic glycolysis regulated by HIF-1α.
-GLUT-1 → regulation of the flux of glucose into cells.
-HK2 → catalysis of the first step of glucose metabolism.
-PKM2 → regulation of rate-limiting step of glycolysis.
-Phosphorylation of PDH complex by PDK → blockage of OXPHOS and promotion of aerobic glycolysis.
-LDH (LDHA): Rapid ATP production, conversion of pyruvate to lactate;

HIF-1α Inhibitors:
-Curcumin: disruption of signaling pathways that stabilize HIF-1α (ie downregulate).
-Resveratrol: downregulate HIF-1α protein accumulation under hypoxic conditions.
-EGCG: modulation of upstream signaling pathways, leading to decreased HIF-1α activity.
-Emodin: reduce HIF-1α expression. (under hypoxia).
-Apigenin: inhibit HIF-1α accumulation.
Scientific Papers found: Click to Expand⟱
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↓,

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

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↓,

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↓,
cycA1↓,
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)↓,

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↑,

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).

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↑,

2319- Api,    Apigenin sensitizes radiotherapy of mouse subcutaneous glioma through attenuations of cell stemness and DNA damage repair by inhibiting NF-κB/HIF-1α-mediated glycolysis
- in-vitro, GBM, NA
Glycolysis↓, Apigenin inhibited the activities of glycolytic enzymes and expressions of nuclear factor kappa B (NF-κB) p65, hypoxia inducible factor-lα (HIF-1α), glucose transporter (GLUT)-1/3 and pyruvate kinase isozyme type M2 (PKM2) proteins in tumor tissues.
NF-kB↓,
p65↓,
Hif1a↓,
GLUT1↓,
GLUT3↓,
PKM2↓,
RadioS↑, Apigenin sensitizes the radiotherapy of SU3-5R cells-inoculated subcutaneous glioma
TumVol↓, Moreover, the tumor weight and relative tumor weight in the three treatment groups were significantly lower than those in the control group
TumW↓,

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,

2299- Api,    Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
- Review, Var, NA
TumCP↓, apigenin reduced proliferation and angiogenesis and significantly suppressed the mRNA and protein expression of HIF-1α, VEGF, and GLUT1 under normoxic and hypoxic conditions
angioG↓,
Hif1a↓,
VEGF↓,
GLUT1↓,
PKM2↓, Moreover, apigenin was suggested to be an allosteric inhibitor of PKM2 due to its ability to ensure a low PKM2/PKM1 ratio and restrain proliferation of colon cancer (HCT116) cells through a blockade of PKM2-dependent glycolysis
Glycolysis↓,

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↑, cleaved
cl‑Casp3↑, cleaved
p‑JAK1↓, phospho
p‑JAK2↓, phospho
p‑STAT3↓, phospho
P53↑,
VEGF↓,
Hif1a↓,
MMP9↓,

958- Api,    Apigenin suppresses tumor angiogenesis and growth via inhibiting HIF-1α expression in non-small cell lung carcinoma
- in-vitro, Lung, NCIH1299
Hif1a↓,
VEGF↓, VEGF-A
VEGFR2↓,
PDGF↓, PDGF-BB/PDGFβR signaling pathway
angioG↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 14

Results for Effect on Cancer/Diseased Cells:
Akt↓,6,   p‑Akt↓,1,   AMPKα↑,1,   angioG↓,4,   AntiAg↑,1,   AntiCan↑,1,   APAF1↑,1,   Apoptosis↑,2,   AR↓,1,   ATF4↑,1,   BAX↑,2,   Bax:Bcl2↑,4,   Bcl-2↓,3,   Bcl-xL↓,2,   BIM↑,1,   BioEnh↑,1,   Ca+2↑,3,   cal2↑,1,   Casp↑,1,   Casp12↑,1,   Casp3↑,3,   cl‑Casp3↑,2,   cl‑Casp7↑,1,   cl‑Casp8↑,2,   Casp9↑,1,   cl‑Casp9↑,1,   Catalase↓,1,   CDK1↓,2,   CDK2↓,1,   CDK4↓,2,   CDK6↓,1,   chemoP↑,2,   ChemoSen↑,3,   CHOP↑,1,   CK2↓,4,   cMyc↓,1,   COX2↓,3,   CSCs↓,2,   cycA1↓,1,   CycB↓,1,   cycD1↓,1,   CycD3↓,1,   Cyt‑c↑,4,   DNAdam↑,2,   Dose∅,4,   E-cadherin↑,2,   eff↑,9,   eff↝,1,   EGFR↓,1,   EMT↓,3,   ER Stress↑,1,   ERK↓,2,   p‑ERK↓,1,   EZH2↓,1,   FAK↓,3,   FASN↓,1,   FOXO3↑,2,   Gli↓,1,   GlucoseCon↓,1,   GLUT1↓,5,   GLUT3↓,1,   Glycolysis↓,2,   GRP78/BiP↑,1,   GSH↓,1,   p‑GSK‐3β↓,2,   Half-Life∅,1,   HDAC↓,3,   HDAC1↓,1,   HDAC3↓,1,   HER2/EBBR2↓,2,   Hif1a↓,12,   HSP90↓,1,   HSPs↓,1,   cl‑IAP2↑,1,   IGF-1↓,2,   IGFBP3↑,1,   IKKα↓,1,   IL1α↓,1,   IL6↓,2,   IL8↓,1,   ITGB4↓,1,   p‑JAK1↓,1,   p‑JAK2↓,1,   p‑JNK↓,1,   MMP↓,3,   MMP2↓,3,   MMP9↓,4,   MMPs↓,3,   mTOR↓,2,   p‑mTOR↓,1,   NADPH↑,1,   Nanog↓,1,   NF-kB↓,3,   NRF2↓,2,   OCT4↓,1,   P21↑,3,   p27↑,1,   p38↑,1,   P53↓,1,   P53↑,4,   p65↓,1,   p‑P70S6K↓,1,   p‑P90RSK↑,1,   cl‑PARP↑,3,   PDGF↓,1,   PI3K↓,4,   PKM2↓,3,   p‑pRB↓,1,   PSA↓,1,   RadioS↑,1,   ROS↑,5,   p‑S6↓,1,   selectivity↑,1,   SIRT3↓,1,   SIRT6↓,1,   SOD↓,1,   STAT3↓,4,   p‑STAT3↓,2,   survivin↓,1,   Telomerase↓,3,   TNF-α↓,1,   TumAuto↑,1,   TumAuto↝,1,   TumCCA↑,6,   TumCI↓,3,   TumCMig↓,2,   TumCP↓,3,   TumMeta↓,1,   TumVol↓,2,   TumW↓,1,   Twist↓,1,   uPA↓,1,   VEGF↓,8,   VEGFR2↓,1,   Wnt/(β-catenin)↓,2,   XIAP↓,1,   β-catenin/ZEB1↓,2,  
Total Targets: 137

Results for Effect on Normal Cells:
Akt↑,1,   AMPK↑,1,   antiOx↑,1,   BioAv↓,2,   BioAv↑,1,   Catalase↓,1,   GPx↑,1,   GSH↑,1,   Half-Life∅,1,   hepatoP↑,1,   Hif1a↓,2,   Inflam↓,3,   MAPK↓,1,   MDA↓,1,   NF-kB↓,1,   NRF2↑,1,   PI3K↓,1,   PKCδ↓,1,   PKM2↓,2,   ROS↓,2,   SOD↑,1,   TAC↑,1,   TGF-β↓,1,   toxicity↓,1,   Vim↓,1,   α-SMA↓,1,  
Total Targets: 26

Scientific Paper Hit Count for: Hif1a, HIF1α/HIF1a
14 Apigenin (mainly Parsley)
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:32  Target#:143  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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