PT  - JOURNAL ARTICLE
AU  - TAECHOWISAN, THONGCHAI
AU  - CHUEN-IM, THANAPORN
AU  - PHUTDHAWONG, WAYA S.
TI  - Molecular Docking and Inhibition of Phosphatidylinositol 3-kinase by Quercetin and Isoquercetin from <em>Streptomyces griseoaurantiacus</em> HNF214
AID  - 10.21873/anticanres.17922
DP  - 2026 Jan 01
TA  - Anticancer Research
PG  - 39--58
VI  - 46
IP  - 1
4099  - http://ar.iiarjournals.org/content/46/1/39.short
4100  - http://ar.iiarjournals.org/content/46/1/39.full
SO  - Anticancer Res2026 Jan 01; 46
AB  - Background/Aim: Standard chemotherapy is limited by severe side effects and drug resistance, driving the need for novel, low-toxicity agents like the flavonoid quercetin. This study aimed to evaluate the anticancer effects of quercetin and isoquercetin from Streptomyces griseoaurantiacus HNF214 against HepG2 cells, focusing on inhibition of the PI3K/Akt/mTOR signaling pathway.Materials and Methods: Quercetin and isoquercetin were purified from microbial culture. Cytotoxicity (MTT assay on HepG2/Vero) and apoptosis markers (MMP, Annexin V, caspase) were assessed. The inhibitory mechanism was studied via ELISA quantification of key proteins (PI3K p85, pAkt, pmTOR), supplemented by molecular docking against the PI3K/AKT/mTOR complex.Results: Both compounds showed concentration-dependent HepG2 inhibition (IC50’s ≈ 380 μg/ml) with minimal Vero cell cytotoxicity. Apoptosis was confirmed by MMP depolarization and a dose-dependent increase in activated caspase-3/9 levels. Mechanistic analysis showed a significant reduction in PI3K p85, leading to decreased pAkt/total Akt and pmTOR/total mTOR ratios. Molecular docking predicted that quercetin binds directly to the active sites of PI3K and AKT.Conclusion: The microbial-derived quercetins effectively induce apoptosis and inhibit HepG2 proliferation by inactivating the PI3K/Akt/mTOR signaling pathway. Quercetin is specifically predicted to directly inhibit PI3K and AKT proteins, underscoring the potential of these compounds as targeted anticancer candidates.