Abstract
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 microM 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.
Highlights
Increasing attention has been paid to primitive medicinal plants and dietary factors to search for new substances with potentially effective anti-cancer activity
Mechanism of α-Mangostin-inducing Apoptosis In our previous study, it was demonstrated that α-mangostin activated caspase-9 and -3 but not -8 in HL60 cells, indicating that α-mangostin may mediate the mitochondrial pathway in the apoptotic process [11]
We demonstrated that α-mangostin induced a cell cycle arrest at G1/S and the subsequent apoptosis via the intrinsic pathway in DLD-1 cells, while a cell cycle arrest by γ-mangostin was at S phase (Figure 4A and B) [14]
Summary
The mangosteen tree has been cultivated for centuries in tropical areas of the world. The white, inner pulp of the mangosteen fruit is highly praised as one of the best tasting of all tropical fruits. The rind (or skin) of the fruit is 0.6-1.0 cm thick and contains a purplish pigment. The inner pulp consists of four to eight juicy, white-colored segments (fruit portion, Figure 1B). The edible portion of the fruit comprises only about 25% of the total volume, whereas the remainder is tough, bitter pericarp which exudes a yellow resin ( the term xanthones or yellow in Greek)(Figure 1B). The mangosteen rind, leaves and bark have been used as folk medicine for thousands of years. The thick mangosteen rind has been and is used for treating catarrh, cystitis, diarrhea, dysentery, eczema, fever, intestinal ailments, pruritis and other skin ailments. It is known that concentrates of mangosteen bark can be used for genito-urinary afflictions and stomatosis
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