Quercetin promises anticancer activity through PI3K-AKT-mTOR pathway: A literature review

Abstract

The PI3K-AKT-mTOR pathway plays a critical role in regulating cellular growth, proliferation, and survival, with its dysregulation being a hallmark of various cancers. Quercetin (QUR), a natural flavonoid, exhibits significant anticancer activity by modulating this pathway. This review examines the anticancer potential of QUR through the PI3K-AKT-mTOR pathway, emphasizing its mechanisms, pharmacokinetics, toxicological profile, clinical relevance, and therapeutic applications. A systematic search of databases, including PubMed and ScienceDirect, was conducted. In vitro and in vivo studies across multiple cancer models were analyzed. QUR inhibits PI3K-AKT-mTOR signaling across cancers, including breast, prostate, pancreatic, brain, and colon. In breast cancer (MCF-7, MDA-MB-231), QUR reduced Akt/mTOR activity at 0.5–100 µM concentrations and 50 mg/kg doses in vivo. Prostate cancer models (LNCaP, PC-3) showed suppression at 200 µM, with efficacy in vivo at 75–200 mg/kg. Pancreatic (MIA PaCa-2), colon (HT-29), and brain cancer (U87) models exhibited similar effects. Despite its promising anticancer effects, QUR’s toxicological profile reveals dose-dependent hepatotoxicity, nephrotoxicity, and potential drug interactions due to cytochrome P450 enzyme inhibition. Clinical evidence suggests QUR possesses antioxidative, anti-inflammatory, and cardioprotective benefits, but its limited bioavailability and safety concerns necessitate further pharmacokinetic optimization. Future research should focus on clinical trials, combination therapies, and advanced delivery systems to enhance therapeutic efficacy while mitigating toxicity.