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↓, ITG">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.
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↓,

1562- Api,    Apigenin protects human melanocytes against oxidative damage by activation of the Nrf2 pathway
- in-vitro, Vit, NA
*SOD↑,
*Catalase↑,
*GPx↑, GSH-Px
*MDA↓,
*NRF2↑, Nrf2 transcription factor, an important regulator oxidative stress and its downstream target genes, was significantly increased by apigenin treatment
*toxicity∅, Apigenin’s non-toxicity

1561- Api,    Apigenin Reactivates Nrf2 Anti-oxidative Stress Signaling in Mouse Skin Epidermal JB6 P + Cells Through Epigenetics Modifications
- in-vivo, Nor, JB6
*NRF2↑, API enhanced the nuclear translocation of Nrf2
*DNMT1↓, API reduced the expression of the DNMT1, DNMT3a, and DNMT3b epigenetic proteins as well as the expression of some HDACs (1–8).
*DNMT3A↓,
*HDAC↓,
*AntiCan↑, results may provide new therapeutic insights into the prevention of skin cancer by dietary phytochemicals.

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

1559- Api,    Dually Active Apigenin-Loaded Nanostructured Lipid Carriers for Cancer Treatment
- in-vitro, Lung, A549 - in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Dose↓, IC50 change from 33ug/mL(APG) to 2.4ug/mL(APG-NLC)
selectivity↑, higher selectivity from cancer to normal cell: see Table 4

1558- Api,    Preparation, characterization and antitumor activity evaluation of apigenin nanoparticles by the liquid antisolvent precipitation technique
- in-vitro, Liver, HepG2
BioAv↑, oral bioavailability of apigenin nanoparticles was about 4.96 times higher than that of the raw apigenin
*toxicity∅, apigenin nanoparticles had no toxic effect on the organs of rats.
eff↑, higher inhibition to HepG2 cells by lower IC50 than that of raw apigenin. In addition, The IC50 values of apigenin nanoparticles and raw apigenin were separately 89.33 and 216.84 μg/mL

1557- Api,    Preparation of apigenin nanocrystals using supercritical antisolvent process for dissolution and bioavailability enhancement
- in-vitro, Nor, NA
*BioAv↑, AP nanocrystals exhibited a significantly decreased tmax, a 3.6-fold higher peak plasma concentration (Cmax) and 3.4-fold higher area under the curve (AUC).

1556- Api,    Dissolution and antioxidant potential of apigenin self nanoemulsifying drug delivery system (SNEDDS) for oral delivery
- Analysis, NA, NA
*BioAv↑, apigenin was developed as SNEDDS to solve its dissolution problem and enhance oral bioavailability
*Dose∅, Smix ratio of 1:1 and concentrations of Gelucire 44/14, Tween 80, and PEG 400 in the ranges of 5–40% w/w, 30–47.5% w/w, and 30–47.5% w/w, respectively, as shown in Table 1.

1555- Api,    USDA Database for the Flavonoid Content of Selected Foods
- Analysis, NA, NA
Dose?, Apigenin in parsley, dried: 4503.50mg/100g(AVG), 1774.60mg/100g(MIN), 13506.22mg/100g(MAX),

1554- Api,    A Review on Flavonoid Apigenin: Dietary Intake, ADME, Antimicrobial Effects, and Interactions with Human Gut Microbiota
- Review, NA, NA
*BioAv↑, apigenin-7-O-glucoside, and acylated derivatives are more water soluble than apigenin [10] and their structures have a major impact on their absorption and bioavailability, with the best bioavailability occurring when apigenin is bound to β-glycoside
*BioAv↑, organic solvents like DMSO [34] and Tween 80 [31] are used to dissolve apigenin prior to their addition to an aqueous solution to increase solubility
*BioAv↑, dietary apigenin is available for metabolism by the gut microbiota
*BioAv↓, Human gut microbiota has been found to harbor enzymes that could degrade apigenin
*eff↑, This study strongly supports that the gut microbiota plays a major role in the metabolism of dietary apigenin.

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

1552- Api,    Apigenin inhibits the growth of colorectal cancer through down-regulation of E2F1/3 by miRNA-215-5p
- in-vitro, CRC, HCT116
Apoptosis↑,
TumCP↓,
miR-215-5p↑, miRNA-215-5p showed markedly increased
TumCCA↑, cell cycle arrest at G0/G1 phase induced by API
E2Fs↓, down-regulation of E2F1/3 by miRNA-215-5p

1551- Api,    Chemotherapeutic effects of Apigenin in breast cancer: Preclinical evidence and molecular mechanisms; enhanced bioavailability by nanoparticles
- Review, NA, NA
*BioAv↑, nanocarriers such as nanocrystals, micelles, liposomes, PLGA, etc., have highlighted the significantly increased bioavailability

1550- Api,    Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential
- Analysis, NA, NA
*BioAv↑, apigenin-phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin
*antiOx↑, exhibited antioxidant potential

1549- Api,  Chemo,    Chemoprotective and chemosensitizing effects of apigenin on cancer therapy
- Review, NA, NA
ChemoSideEff↓, combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents
*toxicity∅, apigenin resulted in no mortality or signs of toxicity in mice/rats at oral doses up to 5000 mg/kg
ChemoSen↑, based on its chemosensitizing effect
eff↑, 5-FU and apigenin at 90 μM and 10 μM concentrations, respectively. This co-therapy led to a significant reduction in ErbB2 and protein kinase B (AKT) expression and AKT phosphorylation as compared to monotherapy
eff↑, molecular analysis of the renal cells demonstrates that pre-treatment by apigenin significantly reduced cisplatin-induced renal injury by anti-oxidant and anti-inflammatory effects.
eff↑, They suggested that metformin and apigenin synergistically inhibited mitochondrial membrane potency and this effect was attributed to a notable increase in ROS levels in cancer cells.

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↓,

1546- Api,    Apigenin in Cancer Prevention and Therapy: A Systematic Review and Meta-Analysis of Animal Models
- Review, NA, NA
TumVol↓, Apigenin reduces tumor volume (SMD=-3.597, 95% CI: -4.502 to -2.691, p<0.001)
TumW↓, tumor-weight (SMD=-2.213, 95% CI: -2.897 to -1.529, p<0.001)
AntiCan↑, tumor number (SMD=-1.081, 95% CI: -1.599 to -0.563, p<0.001) and tumor load (SMD=-1.556, 95% CI: -2.336 to -0.776, p<0.001).
Apoptosis↑, exerts anti-tumor effects mainly by inducing apoptosis/cell-cycle arrest
TumCCA↑,

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)↓,

1544- Api,    The flavone apigenin blocks nuclear translocation of sterol regulatory element-binding protein-2 in the hepatic cells WRL-68
- in-vitro, Nor, WRL68
*SREBF2↓, apigenin prevented SREBP-2 translocation and reduced the downstream gene HMGCR transcription
*HMGCR↓,
*Dose∅, oral dosages of 5.4 mg apigenin/kg body weight would produce a C max value of 16.5 μm in serum
*BioAv?, Given its high bioavailability, its action on cholesterol synthesis could be achievable in this administrative method

1543- Api,    Therapeutical properties of apigenin: a review on the experimental evidence and basic mechanisms
- Review, NA, NA
TNF-α↓,
IL1β↓,
IL6↓,
IL10↓,
COX2↓, blocks the nitric oxide-mediated cyclooxygenase-2 expression
iNOS↓,
Inflam↓,
Dose∅, apigenin contents were reported high in celery and parsley with amounts of 19 and 215 mg per 100 g, respectively
Dose∅, dried parsley contains highest concentration of apigenin (45,035 μg/g). The dried chamomile flowers contain 3,000 to 5,000 μg/g of apigenin.

1542- Api,    Bioavailability of Apigenin from Apiin-Rich Parsley in Humans
- Human, NA, NA
*BioAv?, 2 g blanched parsley/kilogram body weight was consumed. maximum apigenin plasma concentration of 127 +/- 81 nmol/l was reached after 7.2 +/- 1.3 h maximum plasma concentrations were comparably low (0.34 umol/l)
*Half-Life?, peak at 7.2 hours

1541- Api,  EGCG,    Prospective cohort comparison of flavonoid treatment in patients with resected colorectal cancer to prevent recurrence
- Human, NA, NA
OS↑, Among the flavonoid-treated patients with resected colon cancer (n = 14), there was no cancer recurrence and one adenoma developed
Remission↓,
Dose∅, The flavonoid- treated patients took a daily dose of 2 tablets of the flavonoid mixture[24] containing 10 mg apigenin and 10 mg epigallocatechin-gallate per tablet.

1540- Api,    Determination of Total Apigenin in Herbs by Micellar Electrokinetic Chromatography with UV Detection
- Analysis, NA, NA
*BioAv↑, Our assay exhibits about 40-fold lower LOD in comparison with earlier published MEKC procedure

1539- Api,  LT,    Dietary flavones counteract phorbol 12-myristate 13-acetate-induced SREBP-2 processing in hepatic cells
- in-vitro, Liver, HepG2
SREBP2↓, ecreased transcription of SREBP-2 upon the apigenin treatment
eff↑, 25 lM of both flavones could significantly bring down the induced pMEK and pERK.
p‑MEK↓,
p‑ERK↓,

1538- Api,    Enhancing oral bioavailability using preparations of apigenin-loaded W/O/W emulsions: In vitro and in vivo evaluations
- in-vivo, Nor, NA
*BioAv↑, The peak concentrations in the apigenin suspensions and the apigenin-loaded emulsions were 43.55 lg/ml and 395.47 lg/ml, respectively, indicating an approximate ninefold enhancement of oral bioavailability.

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.

1301- Api,    Bcl-2 inhibitor and apigenin worked synergistically in human malignant neuroblastoma cell lines and increased apoptosis with activation of extrinsic and intrinsic pathways
- in-vitro, neuroblastoma, NA
BAX↑,
Bcl-2↓,
Cyt‑c↑, release of cytochrome c into the cytosol
cal2↑,
Casp3↑,

5- Api,    Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer
- in-vitro, Pca, NA
HH↓,
Gli1↓,

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

2664- Api,    Progress in discovery and development of natural inhibitors of histone deacetylases (HDACs) as anti-cancer agents
- Review, Var, NA
HDAC↓, Inhibition of HDAC by apigenin results in H3 and H4 acetylation and hyperacetylation of H3 on the p21/waf1 promoter region.

2641- Api,    Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and beta 4 integrin function in MDA-MB-231 breast cancer cells
- in-vitro, BC, MDA-MB-231
TumCMig↓, apigenin presents the most potent anti-migration and anti-invasion properties
TumCI↓,
ITGB4↓, Apigenin inhibits the HGF-induced clustering of beta 4 integrin at actin-rich adhesive site and lamellipodia through PI3K-dependent manner.

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.

2636- Api,    Apigenin unveiled: an encyclopedic review of its preclinical and clinical insights
- Review, NA, NA
*AntiCan↑, clinical studies are beginning to affirm apigenin's therapeutic benefits, showing positive effects in treating cancer, cardiovascular diseases, diabetes, neurodegenerative disorders, and inflammatory conditions.
*cardioP↑, The findings suggest that apigenin could serve as an effective therapeutic agent to reduce cardiotoxicity caused by Doxorubicin
*neuroP↑,
*Inflam↓,
*antiOx↑, apigenin (5,7,4′-trihydroxyflavone) is a flavonoid that chelates redox-active metals and has antioxidant properties
*hepatoP↑, Overall, the results indicate that apigenin alleviated liver injury by reducing inflammation and oxidative stress via suppression of the non-canonical NF-κB pathway
ChemoSen↑, Apigenin increases the cytotoxicity of sorafenib

2635- Api,  CUR,    Synergistic Effect of Apigenin and Curcumin on Apoptosis, Paraptosis and Autophagy-related Cell Death in HeLa Cells
- in-vitro, Cerv, HeLa
TumCD↑, Treatment with a combination of apigenin and curcumin increased the expression levels of genes related to cell death in HeLa cells 1.29- to 27.6-fold.
eff↑, combination of curcumin and apigenin showed a synergistic anti-tumor effect
TumAuto↑, autophagic cell death, as well as ER stress-associated paraptosis
ER Stress↑,
Paraptosis↑,
GRP78/BiP↓, GRP78 expression was down-regulated, and massive cytoplasmic vacuolization was observed in HeLa cells
Dose↝, combined use of 0.09 μg/μl curcumin and 0.06 μg/μl apigenin showed a synergistic anti-tumor effect

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↑,

2596- Api,  LT,    Natural Nrf2 Inhibitors: A Review of Their Potential for Cancer Treatment
- Review, Var, NA
NRF2↓, In addition, natural compounds such as apigenin, luteolin, chrysin and brusatol have been shown to be potent Nrf2 inhibitors.
chemoP↑, These findings suggest that natural Nrf2 inhibitors could be utilized as chemopreventive and chemotherapeutic agents, as well as tumor sensitizers for conventional radiotherapy and chemotherapy.

2594- Api,  docx,    Targeted hyaluronic acid-based lipid nanoparticle for apigenin delivery to induce Nrf2-dependent apoptosis in lung cancer cells
- in-vitro, Lung, A549
NRF2↓, Apigenin (4,5,7-trihydroxyflavone; APG), as a typically dietary flavonoid, is a potent small molecule inhibitor of Nrf2 that has been studied for its Nrf2 and anticancer activity in different cancers
ChemoSen↑, overcome limitations of the clinical use of APG and improve the efficacy of DTX in lung cancer.

1152- Api,    Does Oral Apigenin Have Real Potential for a Therapeutic Effect in the Context of Human Gastrointestinal and Other Cancers?
- Analysis, Nor, NA
*BioAv↓, We find that oral intake of dietary materials would require heroic ingestion amounts and is not feasible. However, use of supplements of semi-purified apigenin in capsule form could reach target blood levels using amounts that are within the range cu
Half-Life∅, elimination half-life (T1/2) averaging 2.52 ± 0.56h
*BioAv↓, bioavailability is in the region of 30%
Dose∅, Blood and urine samples were taken following a meal consisting of 2g parsley/kg body weight–which was equivalent to ∼17mg of apigenin -> 28–337nmol/L at 6–10h after consumption
eff↑, Apigenin and quercetin enhance their own and each other’s bioavailability by downregulating the activity of ABC transporters
CYP1A2↓, status of apigenin as an inhibitor of CYP1A2, CYP2C9 and CYP3A4
CYP2C9↓,
CYP3A4↓,

2586- Api,  doxoR,    Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway
- in-vitro, HCC, Bel-7402
NRF2↓, APG dramatically reduced Nrf2 expression at both the messenger RNA and protein levels through downregulation of PI3K/Akt pathway, leading to a reduction of Nrf2-downstream genes.
ChemoSen↑, APG can be used as an effective adjuvant sensitizer to prevent chemoresistance by downregulating Nrf2 signaling pathway.

2585- Api,    Apigenin inhibits the proliferation of adenoid cystic carcinoma via suppression of glucose transporter-1
- in-vitro, ACC, NA
GLUT1↓, expression levels of GLUT‑1 were significantly decreased following treatment in a dose- and time-dependent manner.
TumCG↓, inhibition of ACC-2 cell growth by apigenin may be due to the decreased expression of GLUT-1

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

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↓,

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,

2316- Api,    The interaction between apigenin and PKM2 restrains progression of colorectal cancer
- in-vitro, CRC, LS174T - in-vitro, CRC, HCT8 - in-vivo, CRC, NA
TumCP↓, the results proved that the anti-CRC activity of apigenin was positively correlated with pyruvate kinase M2 (PKM2) expression, characterized by the inhibition of cell proliferation and increase of apoptotic effects induced by apigenin in LS-174T cell
PKM2↓, findings reveal that apigenin is worthy of consideration as a promising PKM2 inhibitor for the prevention of CRC
Glycolysis↓, Apigenin restricted the glycolysis of LS-174T and HCT-8 cells by targeting the K433 site of PKM2, thereby playing an anti-CRC role in vivo and in vitro
TumCG↑, apigenin markedly attenuated tumor growth without any adverse effects.
selectivity↑,

2314- Api,    Apigenin Restrains Colon Cancer Cell Proliferation via Targeted Blocking of Pyruvate Kinase M2-Dependent Glycolysis
- in-vitro, Colon, HCT116 - in-vitro, Colon, HT29 - in-vitro, Colon, DLD1
Glycolysis↓, AP could block cellular glycolysis through restraining the tumor-specific pyruvate kinase M2 (PKM2) activity and expression and further significantly induce anti-colon cancer effects.
PKM2:PKM1↓,
β-catenin/ZEB1↓, AP decreases the expression of PKM2 in HCT116 by blocking the B-catenin/c-Myc /PTBP1 pathway
cMyc↓,

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↓,

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%

210- Api,    Apigenin inhibits migration and invasion via modulation of epithelial mesenchymal transition in prostate cancer
- in-vitro, Pca, DU145
EMT↓,
E-cadherin↑,
Snail↓,
Vim↓,

1151- Api,    Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: In vitro and in vivo study
- in-vitro, Pca, PC3 - in-vitro, Pca, 22Rv1 - in-vivo, NA, NA
TumCCA↑,
Apoptosis↑,
HDAC↓, HDAC1 and HDAC3
P21↑,
BAX↑,
TumCG↓,
Bcl-2↓,
Bax:Bcl2↑, shifting the bax/bcl2 ratio in favor of apoptosis
HDAC1↓,
HDAC3↓,

307- Api,    Flavonoids inhibit angiogenic cytokine production by human glioma cells
- in-vitro, GBM, GL-15
TGF-β↓,

275- Api,    Apigenin inhibits the self-renewal capacity of human ovarian cancer SKOV3‑derived sphere-forming cells
- in-vitro, Ovarian, SKOV3
HH↓,
CK2↓, CK2α
Gli1↓,

273- Api,    Apigenin inhibited migration and invasion of human ovarian cancer A2780 cells through focal adhesion kinase
- in-vivo, Ovarian, A2780S
FAK↓,

270- Api,    Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo via inactivation of Akt and activation of JNK
- in-vivo, AML, U937
Akt↓, nactivation of Akt and activation of JNK
JNK↑,
Mcl-1↓,
cl‑Bcl-2↓, cleavage
Casp3↑,
Casp7↑,
Casp9↑,
cl‑PARP↑, cleaved
mTOR↓,
GSK‐3β↓,

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

268- Api,    Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells
- in-vitro, AML, HL-60
Casp3↑,
PARP↑,

244- Api,    Inhibition of the STAT3 signaling pathway contributes to apigenin-mediated anti-metastatic effect in melanoma
- in-vivo, Melanoma, B16-F10 - in-vivo, Melanoma, A375 - in-vivo, Melanoma, G361
STAT3↓,
MMP2↓,
MMP9↓,
VEGF↓,
Twist↓, Twist1
E-cadherin↑,
N-cadherin↓,
EMT↓,

243- Api,    Apigenin Attenuates Melanoma Cell Migration by Inducing Anoikis through Integrin and Focal Adhesion Kinase Inhibition
- in-vitro, Melanoma, A375 - in-vitro, Melanoma, A2058
p‑FAK↓, Apigenin reduced integrin protein levels and inhibited the phosphorylation of focal adhesion kinase (FAK)
ERK↓, ERK1/2
Casp3↑,
PARP↑,
ITGA5↓, revealed that integrin subunits α4, α5, αV, and β3 were clearly downregulated in cell lysates of melanoma cells after apigenin treatment
NA↓,

242- Api,    Apigenin inhibits proliferation and invasion, and induces apoptosis and cell cycle arrest in human melanoma cells
- in-vitro, Melanoma, A375 - in-vitro, Melanoma, C8161
ERK↓,
PI3k/Akt/mTOR↓, Akt/mTOR
Casp3↑, cleaved
PARP↑, cleaved
p‑mTOR↓,
p‑Akt↓,

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

238- Api,    Apigenin inhibits TGF-β-induced VEGF expression in human prostate carcinoma cells via a Smad2/3- and Src-dependent mechanism
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vitro, Pca, C4-2B
VEGF↓,
TGF-β↓,
Src↓,
FAK↓,
Akt↓,
SMAD2↓,
SMAD3↓,

237- Api,    Apigenin blocks IKKα activation and suppresses prostate cancer progression
- in-vivo, Pca, PC3 - in-vivo, Pca, 22Rv1 - in-vivo, Pca, LNCaP - in-vivo, Pca, DU145
IKKα↓,
NF-kB↓,

211- Api,    Suppression of NF-κB and NF-κB-Regulated Gene Expression by Apigenin through IκBα and IKK Pathway in TRAMP Mice
- in-vivo, Pca, NA
IKKα↓,
NF-kB↓,
cycD1↓,
COX2↓,
Bcl-2↓,
Bcl-xL↓,
VEGF↓,
PCNA↓,
BAX↑,

308- Api,    Apigenin Inhibits Cancer Stem Cell-Like Phenotypes in Human Glioblastoma Cells via Suppression of c-Met Signaling
- in-vitro, GBM, U87MG - in-vitro, GBM, U373MG
cMET↓,
Akt↓,
Nanog↓,
SOX2↓, Sox2

208- Api,    Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer
- in-vivo, Pca, PC3 - in-vivo, Pca, DU145
XIAP↓, dose dependent
survivin↓,
Bcl-xL↓,
Bcl-2↓,
BAX↑,

207- Api,    Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells
- in-vitro, Pca, LNCaP
PSA↓,
cycD1↓, cyclinD1 and cyclinD2
cycE↓,
CDK2↓,
CDK4/6↓,
P21↑,
AR↓,

206- Api,    Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress
- in-vitro, Lung, H1299 - in-vitro, Lung, H460 - in-vitro, Lung, A549 - in-vitro, CRC, HCT116 - in-vitro, Melanoma, A375 - in-vitro, Lung, H2030 - in-vitro, CRC, SW480
Glycolysis↓,
NA?,
PGK1↓,
ALDOA↓,
GLUT1↓,
ENO1↓,
ATP↓,
Casp9↑,
Casp3↑,
cl‑PARP↑, cleavage
PI3K/Akt↓,
HK1↓, HK1, HK2
HK2↓,

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↓,

179- Api,    Apigenin induces caspase-dependent apoptosis by inhibiting signal transducer and activator of transcription 3 signaling in HER2-overexpressing SKBR3 breast cancer cells
- in-vitro, BC, NA
cl‑Casp8↑, cleaved
cl‑Casp3↑, cleaved
STAT3↓,
VEGF↓,

178- Api,    Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells
- in-vivo, BC, MDA-MB-231 - in-vitro, BC, T47D
Casp3↑,
cl‑PARP↑, cleavage
Bcl-2↓,
Bcl-xL↓,
BAX↑,

177- Api,    Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression
- in-vitro, BC, MDA-MB-231
Cyc↓, Cyclin A
CycB↓,
CDK1↓,
P21↑,
PCNA↝,
HDAC↓,

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↓,

175- Api,    Apigenin up-regulates transgelin and inhibits invasion and migration of colorectal cancer through decreased phosphorylation of AKT
- vitro+vivo, CRC, SW480 - vitro+vivo, CRC, DLD1 - vitro+vivo, CRC, LS174T
MMP↓,
p‑Akt↓, phosphorylation

174- Api,    Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells
- in-vitro, CRC, SW480 - in-vitro, CRC, DLD1
NEDD9↓,
NA↓,
NA↓,

173- Api,    Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells
- in-vitro, Colon, HCT116
CycB↓,
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↓,

172- Api,    Apigenin suppresses colorectal cancer cell proliferation, migration and invasion via inhibition of the Wnt/β-catenin signaling pathway
- in-vitro, CRC, SW480 - in-vitro, CRC, HTC15
Wnt/(β-catenin)↓,
TCF↓,
LEF1↓, LEF

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↑,

166- Api,    Common botanical compounds inhibit the hedgehog signaling pathway in prostate cancer
HH↓,

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↑,

1150- Api,    Apigenin inhibits the TNFα-induced expression of eNOS and MMP-9 via modulating Akt signalling through oestrogen receptor engagement
- in-vitro, Lung, EAhy926
eNOS↓, Apigenin (50 μM) counteracted the TNFα-induced expression of eNOS and MMP-9 and the TNFα- triggered activation of Akt, p38MAPK and JNK signalling
MMP9↓,
Akt↓,
p38↓,
JNK↓, Apigenin pre-treatment (50 lM) significantly inhibited the TNFa-induced phosphorylation of Akt (Fig. 2a), p38MAPK (Fig. 2b) and JNK

1149- Api,    Apigenin inhibits colonic inflammation and tumorigenesis by suppressing STAT3-NF-κB signaling
- vitro+vivo, IBD, NA
COX2↓,
MPO↓,
NF-kB↓,
STAT3↓,
Inflam↓,

1095- Api,    Apigenin inhibits epithelial-mesenchymal transition of human colon cancer cells through NF-κB/Snail signaling pathway
- Analysis, Colon, NA
Snail↓, Snail inhibitor apigenin
EMT↓,
NF-kB↓,

1077- Api,    Apigenin inhibits COX-2, PGE2, and EP1 and also initiates terminal differentiation in the epidermis of tumor bearing mice
- in-vivo, NMSC, NA
*COX2↓, non-tumor epidermis
COX2∅, apigenin did not inhibit the COX-2 pathway or promote terminal differentiation in the tumors.

1024- Api,  CUR,    Apigenin suppresses PD-L1 expression in melanoma and host dendritic cells to elicit synergistic therapeutic effects
- vitro+vivo, Melanoma, A375 - in-vitro, Melanoma, A2058 - in-vitro, Melanoma, RPMI-7951
TumCG↓,
Apoptosis↑,
PD-L1↓, IFN-γ-induced PD-L1 upregulation was significantly inhibited by flavonoids, especially apigenin
STAT1↓,
tumCV↓,
T-Cell↑, Curcumin and apigenin enhance T cell-mediated melanoma cell killing

1008- Api,    Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW480
Wnt/(β-catenin)↓,
β-catenin/ZEB1↓,
TumAuto↑,
Akt↓,
mTOR↓,
tumCV↓,
TumCCA↑, cell cycle arrest at G2/M phase
TumAuto↑, data suggested the involvement of autophagy in apigenin-induced β-catenin down-regulation during Wnt signaling
p‑Akt↓,
p‑p70S6↓,
p‑4E-BP1↓,

983- Api,    Apigenin acts as a partial agonist action at estrogen receptors in vivo
- in-vivo, NA, NA
ERα↑,
ERβ↑,

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↓,

938- Api,  doxoR,    Apigenin and hesperidin augment the toxic effect of doxorubicin against HepG2 cells
- vitro+vivo, HCC, HepG2
LDHA↓, 5x
HK2↓, 5x

591- Api,  doxoR,    Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines
- in-vitro, AML, Jurkat - in-vitro, AML, THP1
ATP↓,
Casp3↑,
γH2AX↑,

589- Api,  5-FU,    Interactions between dietary flavonoids apigenin or luteolin and chemotherapeutic drugs to potentiate anti-proliferative effect on human pancreatic cancer cells, in vitro
- in-vitro, PC, Bxpc-3
GSK‐3β↓,
NF-kB↓,

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↑,

584- Api,  Cisplatin,    Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms
- in-vivo, Var, NA
Beclin-1↑, 5-FU and/or apigenin caused significant increase in tissue levels of Beclin-1, caspases 3, 9 and JNK activities
Casp3↑,
Casp9↑,
JNK↑,
Mcl-1↓, significant decrease in tumor volume, Mcl-1expression, tissue glutathione peroxidase and total antioxidant capacity
Ki-67↓, alleviated the histopathological changes with significant decrease of Ki-67 proliferation index

583- Api,  Cisplatin,    Apigenin suppresses GLUT-1 and p-AKT expression to enhance the chemosensitivity to cisplatin of laryngeal carcinoma Hep-2 cells: an in vitro study
- in-vitro, Laryn, HEp2
PI3K/Akt↓,
GLUT1↓,
Akt↓,

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↑,

577- Api,  PacT,    Inhibition of IL-6/STAT3 axis and targeting Axl and Tyro3 receptor tyrosine kinases by apigenin circumvent taxol resistance in ovarian cancer cells
- in-vitro, Ovarian, SKOV3
p‑Akt↓, phosphorylation
Bcl-xL↓,
Bcl-2↓,
AXL↓,
Tyro3↓,

421- Api,    Apigenin inhibits HeLa sphere-forming cells through inactivation of casein kinase 2α
- vitro+vivo, Cerv, HeLa
CK2↓, CK2α

419- Api,    Apigenin inhibited hypoxia induced stem cell marker expression in a head and neck squamous cell carcinoma cell line
- in-vitro, SCC, HN30 - in-vitro, SCC, HN8
CD44↓,
Nanog↓,
Endoglin↓, CD105
VEGF↓,

418- Api,    Apigenin inhibits the proliferation and invasion of osteosarcoma cells by suppressing the Wnt/β-catenin signaling pathway
- vitro+vivo, OS, U2OS - vitro+vivo, OS, MG63
β-catenin/ZEB1↓,

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

315- Api,    Apigenin: Selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine pancreatic cancer
- vitro+vivo, PC, Panc02
CK2↓, Apigenin: Selective CK2 inhibitor
CD4+↑,
CD8+↑,
Ikaros↑, (API) stabilized Ikaros expression and prevented Ikaros downregulation

314- Api,    Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis
- in-vitro, SCC, HaCaT - in-vitro, SCC, SCC25
TumCCA↑, G2/M cell cycle arrest.
cycD1↓,
cycE↓,
CDK1/2/5/9∅, CDK1

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↑,

311- Api,    Apigenin inhibits the proliferation of adenoid cystic carcinoma via suppression of glucose transporter-1
- in-vitro, ACC, NA
GLUT1↓,
CC(CDKs/cyclins)↓, CCK-8 (10-160 uM)
TumCCA↑, G2/M cell cycle arrest.

481- CUR,  CHr,  Api,    Flavonoid-induced glutathione depletion: Potential implications for cancer treatment
- in-vitro, Liver, A549 - in-vitro, Pca, PC3 - in-vitro, AML, HL-60
GSH↓, depletion
mtDam↑, mitochondrial dysfunction
MMP↓,
Cyt‑c↑,

2642- Flav,  QC,  Api,  KaempF,  MCT  In Vitro–In Vivo Study of the Impact of Excipient Emulsions on the Bioavailability and Antioxidant Activity of Flavonoids: Influence of the Carrier Oil Type
- in-vitro, Nor, NA - in-vivo, Nor, NA
*BioAv↑, Overall, the bioavailability and antioxidant activity of flavonoids increased when they were coingested with excipient emulsions.
*eff↝, However, in vivo pharmacokinetic experiments showed that the flavonoid concentrations in rat serum were comparable for all carrier oils
BioEnh↑, MCT is the bioenhancer for the Flavonoids (which have low soluability in water)

1025- LT,  Api,    Luteolin and its derivative apigenin suppress the inducible PD-L1 expression to improve anti-tumor immunity in KRAS-mutant lung cancer
- in-vivo, Lung, NA
TumCG↓,
Apoptosis↑,
PD-L1↓, down-regulated the IFN-γ-induced PD-L1 expression
p‑STAT3↓,

1534- LT,  Api,  EGCG,  RES,    Plant polyphenol induced cell death in human cancer cells involves mobilization of intracellular copper ions and reactive oxygen species generation: a mechanism for cancer chemopreventive action
- in-vitro, Nor, MCF10 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468 - in-vitro, PC, Bxpc-3
TumCP↓,
Apoptosis↑,
eff↓, cell death is prevented to a significant extent by cuprous chelator neocuproine and reactive oxygen species scavengers
*toxicity↑, normal breast epithelial cells, cultured in a medium supplemented with copper, become sensitized to polyphenol-induced growth inhibition.
Dose?, apigenin at 5uM promoted growth in MCF10A cells and PC3 cancer cells. This could be because polyphenols at lower concentrations are known to be associated with cell proliferation [21], while behaving as prooxidants at high concentrations
eff↓, Apigenin- and luteolin-induced antiproliferation and apoptosis in cancer cells is inhibited by cuprous chelator but not by iron and zinc chelators
eff↓, EGCG and resveratrol, similar to that of the flavones luteolin and apigenin, also involves the mobilization of endogenous copper and consequent prooxidant effect leading to cell death.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 119

Results for Effect on Cancer/Diseased Cells:
p‑4E-BP1↓,1,   AIF↑,1,   Akt↓,17,   p‑Akt↓,8,   ALDOA↓,1,   AMPK↑,1,   AMPKα↑,1,   angioG↓,5,   AntiAg↑,1,   AntiCan↑,2,   AntiTum↑,1,   APAF1↑,2,   Apoptosis↑,17,   AR↓,2,   ATF4↑,2,   p‑ATM↑,1,   ATP↓,3,   AVOs↑,1,   AXL↓,1,   Bak↑,1,   BAX↑,13,   BAX∅,1,   Bax:Bcl2↑,7,   Bcl-2↓,14,   Bcl-2∅,1,   cl‑Bcl-2↓,1,   Bcl-xL↓,8,   Bcl-xL∅,1,   Beclin-1↑,2,   cl‑BID↑,1,   BIM↑,2,   BioAv↓,1,   BioAv↑,1,   BioEnh↑,2,   Ca+2↑,6,   cal2↑,2,   Casp↑,3,   Casp12↑,1,   Casp3↑,18,   Casp3∅,1,   cl‑Casp3↑,5,   proCasp3↓,1,   Casp7↑,1,   cl‑Casp7↑,1,   Casp8↑,4,   Casp8∅,1,   cl‑Casp8↑,5,   proCasp8↓,1,   Casp9↑,8,   cl‑Casp9↑,2,   proCasp9↓,1,   Catalase↓,1,   Catalase↑,1,   CC(CDKs/cyclins)↓,1,   CD4+↑,1,   CD44↓,1,   CD8+↑,1,   cDC2↓,2,   p‑cDC2↑,1,   CDC25↓,3,   p‑CDC25↑,1,   CDK1↓,3,   CDK1/2/5/9∅,1,   CDK2↓,3,   CDK4↓,2,   CDK4/6↓,2,   CDK6↓,1,   chemoP↑,5,   ChemoSen↑,9,   ChemoSen∅,1,   ChemoSideEff↓,1,   p‑CHK1↑,1,   CHOP↑,3,   cJun↓,1,   CK2↓,8,   cMET↓,1,   cMyc↓,2,   COX2↓,6,   COX2∅,1,   CSCs↓,2,   Cyc↓,2,   cycA1↓,1,   CycB↓,3,   cycD1↓,4,   CycD3↓,1,   cycE↓,2,   CYP1A2↓,1,   CYP2C9↓,1,   CYP3A4↓,1,   Cyt‑c↑,13,   DNAdam↑,6,   Dose?,2,   Dose↓,1,   Dose↝,1,   Dose∅,9,   DR5↑,2,   E-cadherin↑,4,   E2Fs↓,1,   eff↓,7,   eff↑,18,   eff↝,2,   EGFR↓,2,   EMT↓,6,   Endoglin↓,1,   ENO1↓,1,   eNOS↓,1,   ER Stress↓,1,   ER Stress↑,5,   ERK↓,6,   p‑ERK↓,3,   p‑ERK⇅,1,   ERα↑,1,   ERβ↑,1,   EZH2↓,1,   FAK↓,5,   p‑FAK↓,1,   FASN↓,1,   FOXO↓,1,   FOXO3↑,2,   Gli↓,1,   Gli1↓,2,   glucose↓,1,   GlucoseCon↓,1,   GLUT1↓,10,   GLUT3↓,1,   Glycolysis↓,5,   GRP78/BiP↓,1,   GRP78/BiP↑,1,   GSH↓,4,   GSK‐3β↓,2,   p‑GSK‐3β↓,2,   Half-Life∅,2,   HDAC↓,6,   HDAC1↓,2,   HDAC3↓,2,   HER2/EBBR2↓,2,   HH↓,3,   Hif1a↓,12,   HK1↓,1,   HK2↓,2,   HSP90↓,1,   HSPs↓,1,   cl‑IAP2↑,1,   IGF-1↓,2,   IGFBP3↑,1,   Ikaros↑,1,   IKKα↓,3,   IL10↓,1,   IL1α↓,1,   IL1β↓,1,   IL6↓,3,   IL8↓,1,   Inflam↓,2,   iNOS↓,1,   ITGA5↓,1,   ITGB4↓,2,   JAK↓,1,   p‑JAK↓,1,   p‑JAK1↓,1,   p‑JAK2↓,2,   JNK↓,1,   JNK↑,3,   p‑JNK↓,2,   Ki-67↓,1,   LC3B↑,1,   LC3s↝,1,   LDHA↓,1,   LEF1↓,1,   lipid-P↑,1,   MAPK↓,1,   MAPK↝,1,   Mcl-1↓,2,   MDA↑,1,   MDM2↓,1,   p‑MEK↓,1,   miR-215-5p↑,1,   MLKL↑,2,   p‑MLKL↓,1,   MMP↓,12,   MMP↑,1,   MMP2↓,6,   MMP9↓,8,   MMPs↓,3,   MPO↓,1,   mtDam↑,2,   mTOR↓,6,   p‑mTOR↓,2,   N-cadherin↓,1,   NA?,1,   NA↓,3,   NADPH↑,1,   Nanog↓,3,   Necroptosis↑,2,   NEDD9↓,1,   neuroP↑,1,   NF-kB↓,14,   NRF2↓,6,   OCT4↓,1,   OS↑,2,   P21↑,12,   p27↑,2,   p38↓,1,   p38↑,1,   p‑p38↑,1,   p50↓,1,   P53↓,1,   P53↑,12,   p‑P53↑,2,   p62↓,1,   p62↑,1,   p65↓,2,   p‑p70S6↓,1,   p‑P70S6K↓,1,   p‑P90RSK↑,1,   Paraptosis↑,1,   PARP↑,4,   p‑PARP↑,1,   cl‑PARP↑,9,   cl‑PARP1↑,1,   PCNA↓,1,   PCNA↝,1,   PD-L1↓,2,   PDGF↓,1,   PGK1↓,1,   PI3K↓,10,   p‑PI3K↓,1,   PI3K/Akt↓,3,   PI3k/Akt/mTOR↓,1,   PKM2↓,4,   PKM2:PKM1↓,1,   p‑pRB↓,1,   PSA↓,2,   radioP↑,2,   RadioS↑,3,   Remission↓,1,   RenoP↑,1,   RIP3↑,1,   p‑RIP3↑,2,   ROS↓,1,   ROS↑,18,   p‑S6↓,1,   selectivity↓,1,   selectivity↑,8,   Sharpin↓,1,   SIRT3↓,1,   SIRT6↓,1,   Slug↓,2,   SMAD2↓,1,   SMAD3↓,1,   Snail↓,5,   SOD↓,1,   SOX2↓,1,   Src↓,1,   SREBP2↓,1,   STAT↓,1,   p‑STAT↓,1,   STAT1↓,1,   STAT3↓,9,   p‑STAT3↓,4,   survivin↓,3,   T-Cell↑,1,   TCF↓,1,   Telomerase↓,3,   TGF-β↓,2,   TNF-α↓,2,   TNF-α∅,1,   TumAuto↑,7,   TumAuto↝,1,   TumCCA↑,19,   TumCD↑,2,   TumCG↓,6,   TumCG↑,2,   TumCI↓,7,   TumCMig↓,6,   TumCP↓,10,   tumCV↓,4,   TumMeta↓,1,   TumVol↓,4,   TumW↓,4,   Twist↓,2,   Tyro3↓,1,   uPA↓,1,   UPR↑,1,   VEGF↓,15,   VEGFR2↓,1,   Vim↓,1,   Wnt↓,1,   Wnt/(β-catenin)↓,5,   XIAP↓,2,   β-catenin/ZEB1↓,6,   γH2AX↑,1,  
Total Targets: 291

Results for Effect on Normal Cells:
Akt↑,1,   AMPK↑,1,   AntiCan↑,2,   antiOx↑,4,   BioAv?,2,   BioAv↓,5,   BioAv↑,11,   cardioP↑,1,   cl‑Casp3↓,1,   Catalase↓,1,   Catalase↑,1,   CHOP↓,1,   COX2↓,2,   DNMT1↓,1,   DNMT3A↓,1,   Dose∅,2,   eff↑,1,   eff↝,1,   GPx↑,2,   GSH↑,1,   Half-Life?,1,   Half-Life∅,1,   HDAC↓,1,   hepatoP↑,2,   Hif1a↓,2,   HMGCR↓,1,   Inflam↓,5,   Insulin↑,1,   MAPK↓,1,   MDA↓,2,   neuroP↑,1,   NF-kB↓,1,   NRF2↑,3,   other↝,1,   PI3K↓,1,   PKCδ↓,1,   PKM2↓,2,   ROS↓,4,   ROS∅,1,   SOD↑,2,   SREBF2↓,1,   TAC↑,1,   TGF-β↓,1,   toxicity↓,2,   toxicity↑,1,   toxicity∅,3,   TXNIP↓,1,   Vim↓,1,   α-SMA↓,1,  
Total Targets: 49

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:32  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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