Inhibition of mTOR Signaling by Quercetin in Cancer Treatment and Prevention

Ansgar      Bruning

Abstract

Quercetin is an abundant micronutrient in our daily diet. Several beneficial health effects are associated with the dietary uptake of this bioflavonoid, including alleviating effects on chronic inflammation and atherosclerosis. A variety of in vitro data indicate a possible use of quercetin for cancer treatment purposes through its interaction with multiple cancer-related pathways. Among these, recent data reveal that quercetin can inhibit mTOR activity in cancer cells. Inhibition of the mTOR signaling pathway by quercetin has directly been described and can further be deduced from its interference with PI3K-dependent Akt stimulation, AMP-dependent protein kinase activation and hamartin upregulation. The ability of quercetin to interfere with both mTOR activity and activation of the PI3K/Akt signaling pathway gives quercetin the advantage to function as a dual-specific mTOR/PI3K inhibitor. The mTOR complex, often hyperactivated in cancer, is a crucial regulator of homeostasis controlling essential pathways leading to cell growth, protein biosynthesis and autophagy. The ability of quercetin to inhibit mTOR activity by multiple pathways makes this otherwise safe bioflavonoid an interesting tool for the treatment of cancers and other diseases associated with mTOR deregulation.

Keywords: Quercetin, autophagy, mTOR, AMPK, Akt, proteasome, anti-oxidant, cancer.