Mangosteen Studies(Page 2)Mangosteen Studies - 3Nakatani K, Nakahata N, Arakawa T, Yasuda H, Ohizumi Y. Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, 980-8578, Sendai, Japan. The fruit hull of mangosteen, Garcinia mangostana L., has been used for many years as a medicine for treatment of skin infection, wounds, and diarrhea in Southeast Asia. In the present study, we examined the effect of gamma-mangostin, a tetraoxygenated diprenylated xanthone contained in mangosteen, on arachidonic acid (AA) cascade in C6 rat glioma cells. gamma-Mangostin had a potent inhibitory activity of prostaglandin E2 (PGE2) release induced by A23187, a Ca2+ ionophore. The inhibition was concentration-dependent, with the IC50 value of about 5 microM. gamma-Mangostin had no inhibitory effect on A23187-induced phosphorylation of p42/p44 extracellular signal regulated kinase/mitogen-activated protein kinase or on the liberation of [14C]-AA from the cells labeled with [14C]-AA. However, gamma-mangostin concentration-dependently inhibited the conversion of AA to PGE2 in microsomal preparations, showing its possible inhibition of cyclooxygenase (COX). In enzyme assay in vitro, gamma-mangostin inhibited the activities of both constitutive COX (COX-1) and inducible COX (COX-2) in a concentration-dependent manner, with the IC50 values of about 0.8 and 2 microM, respectively. Lineweaver-Burk plot analysis indicated that gamma-mangostin competitively inhibited the activities of both COX-1 and -2. This study is a first demonstration that gamma-mangostin, a xanthone derivative, directly inhibits COX activity. Mangosteen Studies - 4Anti-cancer effects of xanthones from pericarps of mangosteen. Akao Y, Nakagawa Y, Iinuma M, Nozawa Y. Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan; Tel: +81-583-71-4646. Mangosteen, Garcinia mangostana Linn, is a tree found in South East Asia, and its pericarps have been used as traditional medicine. Phytochemical studies have shown that they contain a variety of secondary metabolites, such as oxygenated and prenylated xanthones. Recent studies revealed that these xanthones exhibited a variety of biological activities containing anti-inflammatory, anti-bacterial, and anti-cancer effects. We previously investigated the anti-proliferative effects of four prenylated xanthones from the pericarps; alpha-mangostin, beta-mangostin, gamma-mangostin, and methoxy-beta-mangostin in various human cancer cells. These xanthones are different in the number of hydroxyl and methoxy groups. Except for methoxy-beta-mangostin, the other three xanthones strongly inhibited cell growth at low concentrations from 5 to 20 muM in human colon cancer DLD-1 cells. Our recent study focused on the mechanism of alpha-mangostin-induced growth inhibition in DLD-1 cells. It was shown that the anti-proliferative effects of the xanthones were associated with cell-cycle arrest by affecting the expression of cyclins, cdc2, and p27; G1 arrest by alpha-mangostin and beta-Mangostin, and S arrest by gamma-mangostin. alpha-Mangostin found to induce apoptosis through the activation of intrinsic pathway following the down-regulation of signaling cascades involving MAP kinases and the serine/threonine kinase Akt. Synergistic effects by the combined treatment of alpha-mangostin and anti-cancer drug 5-FU was to be noted. alpha-Mangostin was found to have a cancer preventive effect in rat carcinogenesis bioassay and the extract from pericarps, which contains mainly alpha-mangostin and gamma-mangostin, exhibited an enhancement of NK cell activity in a mouse model. These findings could provide a relevant basis for the development of xanthones as an agent for cancer prevention and the combination therapy with anti-cancer drugs. Research Information RequestTo receive updated research information as it becomes available, please fill out the form below. Your e-mail address will not be sold, rented or exchanged.
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