The Effect of Gartanin, a Naturally Occurring Xanthone in Mangosteen Juice, on the mTOR Pathway, Autophagy, Apoptosis, and the Growth of Human Urinary Bladder Cancer Cell Lines

Garcinia mangostana, often referred to as mangosteen, is a fruit grown in Southeast Asia and has been used for centuries as a local beverage and natural medicine. Its bioactive compounds, xanthones (i.e., gartanin, -mangostin, etc), have reported effects on ailments ranging from skin infections and inflammation to urinary tract infections. We demonstrate that mangosteen xanthones (i.e., gartanin and -mangostin) at pharmacologically achievable concentrations inhibit the growth of cancer cell lines from different stages of human urinary bladder cancer. The growth inhibitory effects of gartanin in mouse embryonic fibroblasts are at least in part dependent on the existence of p53 or TSC1. Indeed, further studies have shown that gartanin treatment of bladder cancer cell lines T24 and RT4 resulted in a marked suppression of p70S6 and 4E-BP1 expression and induction of autophagy, suggesting the inhibition of the mTOR pathway. In addition, gartanin downregulated the expression of Bcl-2 and activated the p53 pathway leading to apoptosis induction. Together, these results suggested that gartanin is a multiple targeting agent that is suitable for further study into its chemopreventive properties for human urinary bladder cancer.