α-Mangostin, a xanthone from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growth
Menée sur des cellules humaines de cancer de la prostate et à l'aide d'une xénogreffe, cette étude montre que l'alpha-mangoustine, une xanthone provenant du fruit du mangoustan (arbuste cultivé en Malaisie et dans le Sud de l'Inde), peut inhiber la croissance tumorale
There is a need to characterize promising dietary agents for chemoprevention and therapy of prostate cancer (PCa). We examined the anti-cancer effect of α-mangostin, derived from the mangosteen fruit, in human prostate cancer cells and its role in targeting cell cycle related proteins involved in prostate carcinogenesis. Using an MTT assay we found that α-mangostin significantly decreasesPCa cell viability in a dose dependent manner. Further analysis using flow cytometry identified cell cycle arrest along with apoptosis. To establish a more precise mechanism of action, we performed a cell free biochemical kinase assay against multiple cyclins/CDKs involved in cell cycle progression; the most significant inhibition in the cell free based assays was CDK4, a critical component of the G1 phase.Through molecular modeling we evaluated α-mangostin against the ATP binding pocket of CDK4, and propose three possible orientations that may result in CDK4 inhibition. We then performed an in vivo animal study to evaluate the ability of α-mangostin to suppress tumor growth. Athymic nude mice were implanted with 22Rv1 cells and treated with vehicle or α-mangostin (100 mg/kg) by oral gavage. At the conclusion of the study mice in the control cohort had a tumor volume of 1190 mm3, while the treatment groupshad a tumor volume of 410 mm3(p < 0.01). The ability of α-mangostin to inhibit prostate cancer in vitro and in vivo suggests α-mangostin may be a novel agent for the management of PCa.
http://carcin.oxfordjournals.org/content/early/2011/12/09/carcin.bgr291.abstract