Xanthones from the mangosteen fruit (Garcinia mangostana) disrupt androgen receptor functionality in prostate cancer

The purple mangosteen fruit (Garcinia mangostana), native to Southeast Asia, has long been used in traditional medicine, however recent data has shown that xanthones, a class of chemical compounds isolated from the mangosteen, display anti-cancer activity [1]. α-Mangostin is the most abundant xanthone with more than 80 that have been isolated and identified from the fruit, roots, bark, and leaves of the mangosteen. Androgen receptor (AR) degradation is a novel strategy that would help to overcome the rising drug resistance to FDA approved anti-androgens that are used to treat prostate cancer [2]. Our data suggests that α-mangostin interacts with the androgen receptor, and may disrupt AR functionality and degrade AR. Two different prostate cancer cell lines (22Rν1 and LNCaP) were used to evaluate efficacy and perform mechanism of action studies. Xanthone treatments promote a dose and time dependent decrease in AR, along with an additional increase in chaperone proteins involved in degradation. Additionally, there is a reduction in the phosphorylation profile of AR, suggesting these actions inhibit the nuclear translocation of AR. Consequently, these actions inhibit the transcription of downstream genes that are necessary for cell growth and proliferation. Our results suggest that α-mangostin promotes AR degradation by inhibiting nuclear translocation and may be effective against drug resistant prostate cancer cases.

• References

• 1 Ovalle-Magallanes B, Eugenio-Pérez D, Pedraza-Chaverri J. Medicinal properties of mangosteen (Garcinia mangostana L.): A comprehensive update. Food Chem Toxicol 2017; 109 (01) : 102-122.
• 2 Li G, Petiwala SM, Yan M. et al. Gartanin, an isoprenylated xanthone from the mangosteen fruit (Garcinia mangostana), is an androgen receptor degradation enhancer. Mol Nutr Food Res 2016; 60: 1458-1469.