| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-925 | |
| Phytochemical name or plant extracts | Apigenin | |
| PMID | 2749004 | |
| Literature evidence | Flavone, 6-hydroxyflavone and 4',5,7-trihydroxyflavone (apigenin) were the most potent with IC50 of 2.7, 3.4, and 3.5 micrograms/ml, respectively. | |
| IUPAC name | 5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one | |
| Phytochemicals’ class or type of plant extracts | Flavonoid | |
| Source of phytochemicals or plant Extracts | Clerodendrum viscosum | |
| Geographical availability | Andaman Is., Assam, Bangladesh, China South-Central, East Himalaya, India, Laos, Myanmar, Nepal, Nicobar Is., Philippines, Sri Lanka, Thailand | |
| Plant parts | Leaves | |
| Other cancers | Breast cancer, Prostate cancer, Colon cancer, Lung cancer, Cervical cancer, Bronchogenic cancer, Epidermoid cancer | |
| Target gene or protein | Cyclin D1, Cyclin D3, CDK4, HER2/neu , AKT, CTSS, C3, LAMC2, TLR2, GPRC5B, CNTNAP1, CLDN1, NFATC2, CXCL10, CXCL11, IRAK3, NR3C2, IL32, IL-24, SLIT2, TMEM132A, TMEM171, STAP2, MLKL, KDR, BMPER, KLHL36, STAT-3, YAP/TAZ, CTGF, CYR61, Caspase 3, VEGF, Progestrone receptor, PI3K, JAK3, PLD2, CYP1A1,CYP1B1 | |
| Gene or Protein evidence | Furthermore, apigenin downregulated cyclin D1, D3 and Cdk4 and increased p27 protein levels. We have shown that exposure of the HER2/neu-overexpressing breast cancer cells to apigenin resulted in induction of apoptosis by depleting HER2/neu protein and, in turn, suppressing the signaling of the HER2/HER3-PI3K/Akt pathway. Apigenin-treated MDA-MB-468 cells also showed reduced phosphorylation of Akt (protein kinase B), which is an essential effector serine/threonine kinase in the phosphatidylinositide 3-kinase pathway that promotes tumor growth and progression. In addition, these data further establish more than a 65% reduction by apigenin for the following transcripts which were also up-regulated by TNFα: cathepsin S (CTSS), complement C3 (C3), laminin subunit gamma 2 (LAMC2), (TLR2), toll-like receptor 2 G protein-coupled receptor class C group 5 member B (GPRC5B), contactin-associated protein 1 (CNTNAP1), claudin 1 (CLDN1), nuclear factor of activated T-cells 2 (NFATC2), C-X-C motif chemokine ligand 10 (CXCL10), CXCL11, interleukin 1 receptor-associated kinase 3 (IRAK3), nuclear receptor subfamily 3 group C member 2 (NR3C2), interleukin 32 (IL32), IL24, slit guidance ligand 2 (SLIT2), transmembrane protein 132A (TMEM132A), TMEM171, signal transducing adaptor family member 2 (STAP2), mixed lineage kinase domain-like pseudokinase (MLKL), kinase insert domain receptor (KDR), BMP-binding endothelial regulator (BMPER), and kelch-like family member 36 (KLHL36). Apigenin decreased STAT3 activation (p‑STAT3) and its nuclear translocation and inhibited the secretion of VEGF and MMP‑9, which are STAT3 target genes. Our mechanism study demonstrated that apigenin decreased YAP/TAZ activity and the expression of target genes, such as CTGF and CYR61, in TNBC cells. Moreover, apigenin inhibited the growth of TNBC patient-derived organoids at an in vivo achievable concentration., Apigenin sensitized spheroids to doxorubicin-induced DNA damage, triggering caspase-9-mediated intrinsic apoptotic pathway and caspase-3 activity. Inhibition of VEGF release by flavonoids, tocopherols, and lovastatin in these models of neoplastic cells suggests a novel mechanism for mammary cancer prevention. We previously identified apigenin as a potential phytoprogestin, a natural product with a chemical scaffold that interacts with the progesterone receptor (PR). Furthermore, serum-deprived cells in culture show an upregulated EGFR/JAK3/PLD2-PA system and are especially sensitive to a combination of JAK3 and PLD2 enzymatic activity inhibitors (30nM apigenin and 300nM 5-fluoro-2-indolyl des-chlorohalopemide (FIPI), respectively). Taken collectively, the data demonstrate that the metabolism of hydroxylated flavonoids by cytochrome P450 CYP1 enzymes, notably CYP1A1 and CYP1B1, can enhance their antiproliferative activity in breast cancer cells. | |
| Target pathways | Mitochondria/Caspase-Pathway PI3K/Akt pathway HER2/HER3-PI3K/Akt pathway Phosphatidylinositide 3-kinase pathway Caspase-9-mediated intrinsic apoptotic pathway p53 and caspase-cascade signaling pathway Transcription 3 (STAT3) signaling pathway | |
| IC50 | 56.72 ± 2.35 µM against MCF-7 | |
| Potency | EC50 = 1.0 microM against MCF-7. 1. The rank order of inhibitory potency was naringin > rutin > alpha-tocopheryl succinate (alpha-TOS) > lovastatin > apigenin > genistein > alpha-tocopherol >or= kaempferol > gamma-tocopherol, chrysin and curcumin were inactive except at a concentration of 100 micromol/L. 2. Flow cytometry analysis revealed that protoapigenone induced apoptosis with 10-fold greater potency than apigenin. 3. However, in mammalian assay, apigenin was found to be more ERbeta-selective than genistein, which has equal potency in inducing transactivation through ERalpha and ERbeta. 4. Flavone, apigenin and luteolin showed potent inhibitory effects on the proliferation of Hs578T, MDA-MB-231 and MCF-7 breast cancer cells in a concentration and time-dependent manner. 5. All the prepared apigenin analogs exhibited more potent activities than the parent apigenin. 6. Kaempferol, genistein, and apigenin were more potent anti-androgens than bisphenols A or F. 6. Results show that apigenin presents the most potent anti-migration and anti-invasion properties by Boyden chamber assay. 7. Protoapigenone, a natural derivative of the flavonoid apigenin, has been shown to exhibit potent antitumor activity in vitro and in vivo, the precise mechanism of action, however, is not fully elucidated. | |
| Cell line/ mice model | MDA-MB-453, T47D, ZR-75-1, PC-3, MCF-7, HT-29, HeLa, A549, MDA-MB-231, ChaGo-I , NIH/3T3, A431, MDA-MB-468, Hs578T, SKBR-3 | |
| Additional information | In addition, the apigenin-induced accumulation of the cell population in the G(2)/M phase resulted in a decrease in CDK1 together with cyclin A and cyclin B. In an additional study, apigenin also increased the accumulation of p53 and further enhanced the level of p21(Cip1), with no change in p27(Kip1). In addition, apigenin activated caspase-3, which functions downstream of caspase-9. In addition, AI and apigenin time- and dose-dependently down regulated the matrix metalloproteinase (MMP)-9 enzymatic activities and its mRNA expression. In addition, luteolin, the major metabolite of apigenin, inhibited IFN-γ-induced PD-L1 expression by MDA-MB-468 cells. In addition, apigenin upregulated p21WAF1/CIP1 and increased the interaction of p21WAF1/CIP1 with proliferating cell nuclear antigen (PCNA), which inhibits cell cycle progression. In addition to MDA-MB-231 cells, apigenin exhibits inhibitory effect on HGF-induced Akt phosphorylation in hepatoma SK-Hep1 cells and lung carcinoma A549 cells. | |
| PubChem ID | 5280443 | |
| Additional PMIDs | 16702307 18656338 19430615 19885610 25299247 26483970 26675309 29142403 29593542 31404596 32059077 33054206 33466512 33662771 33556877 11588896 18596662 16860978 35210693 32460177 32208740 21031625 23519250 29215574 30870993 16579729 22634262 25560707 27137679 27933483 32552791 10923837 34595891 33594798 19428344 22272829 25183275 27232543 28366842 10801845 27378243 15110097 30479839 15703835 17154505 19666078 28396216 28656316 30678243 31659097 31877350 32715386 33011162 29981677 9770719 23592903 25019465 26872304 10989984 15620704 17961621 19288491 20686818 22071170 23238254 23189742 23973682 25327419 29097115 30600693 33678040 18239283 17132221 16206043 21912610 29736565 8105867 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:862482-1 | |
| Safety | NA |