The purple mangosteen (Garcinia mangostana): Defining the anticancer potential of selected xanthones.

The purple mangosteen (Garcinia mangostana) is a popular Southeast Asian fruit that has been used traditionally for its health promoting benefits for years. Unique to the mangosteen are a class of phytochemicals known as xanthones that have been reported to display significant anti-cancer and anti-tumor activities, specifically through the promotion of apoptosis, targeting of specific cancer-related proteins, or modulation of cell signaling pathways. α-Mangostin, the most abundant xanthone isolated from the mangosteen, has received substantial attention as it has proven to be a potent phytochemical, specifically as an anticancer agent, in numerous different cancer cell studies and cancer animal models. While the mechanisms for these anticancer effects have been reported in many studies, lesser xanthones, including gartanin, ß-mangostin, γ-mangostin, garcinone C, and garcinone E, and mangosteen extracts from the pericarp, roots, rind, and stem show promise for their anticancer activity but their mechanisms of action are not as well developed and remain to be determined. Mangosteen products appear safe and have been well tolerated in human clinical trials where they show antioxidant activity, though their clinical anticancer activity has not yet been evaluated. This review summarizes the work that has been done to explore and explain the anticancer and antitumor activities of α-mangostin, lesser xanthones, and mangosteen extracts in vitro, in vivo, and in humans in various cancers.

Acetyl- and O-alkyl- derivatives of ß-mangostin from Garcinia mangostana and their anti-inflammatory activities.

Pure ß-mangostin (1) was isolated from the stem bark of Garcinia mangostana L. One monoacetate (2) and five O-alkylated ß-mangostin derivatives (3-7) were synthesised from ß-mangostin. The structures of these compounds were elucidated and determined using spectroscopic techniques such as 1D NMR and MS. The cytotoxicities and anti-inflammatory activities of these five compounds against RAW cell 264.7 were tested. The structural-activity relationship studies indicated that ß-mangostin showed a significant activity against the LPS-induced RAW cell 264.7, while the acetyl- as well as the O-alkyl- ß-mangostin derivatives did not give good activity. Naturally occurring ß-mangostin demonstrated comparatively better anti-inflammatory activity than its synthetic counterparts.

Depigmentation of α-melanocyte-stimulating hormone-treated melanoma cells by ß-mangostin is mediated by selective autophagy.

Melanogenesis is a key pathway for the regulation of skin pigmentation and the development of skin-lightening/skin-whitening drugs or cosmetics. In this study, we found that ß-mangostin from seedcases of Garcinia mangostana inhibited α-melanocyte-stimulating hormone (α-MSH)-mediated melanogenesis in B16F10 melanoma cells and a three-dimensional human skin model. ß-Mangostin significantly inhibited the protein level of tyrosinase induced by α-MSH in UPS (ubiquitin proteasome system)-independent and lysosome-dependent manner. The inhibition of autophagy by 3-methyladenine treatment or ATG5 knockdown effectively recovered premelanosome protein as well as tyrosinase degraded by the ß-mangostin treatment. However, rapamycin, a representative non-selective autophagy inducer, triggered autophagy in α-MSH-stimulated cells, which was characterized by a considerable decrease in p62, but it was unable to inhibit melanogenesis. Melanosome-engulfing autophagosomes were observed using transmission electron microscopy. Furthermore, previously formed melanin could be degraded effectively in an autophagy-dependent manner in ß-mangostin-treated cells. Taken together, our results suggest that ß-mangostin inhibits the melanogenesis induced by α-MSH via an autophagy-dependent mechanism, and thus, the depigmentation effect of ß-mangostin may depend on autophagy targeted at the melanosome rather than non-selective autophagy.