Inhibitory activity of metabolites from mangosteen roots Garcinia mangostana L. on hepatocellular carcinoma and colon cancer cell growth

Abstract

Liver cancer is one of the most common deadliest diseases both worldwide and in Thailand. Because of its rich and dual blood supply, malignant tumors in the liver could grow proliferative and rapidly spread to another organ. This process was called Metastasis, the major cause of human death. Mangosteen (Garcinia mangostana L.) generally known as a queen of fruits, has been widely studied in medicinal applications for many decades, due to plenty of bioactive metabolites such as xanthones as a major component. Nonetheless, reports about bioactivities of minor components were barely known. In this study, metabolites isolated from mangosteen roots were evaluated their cytotoxic property and antiproliferative against hepatocellular carcinoma (HepG2 and Huh-7) and colon (Caco2 and HCT-116) cancer cells. The remarkable compounds were further investigated in molecular biology, including cell migration, apoptosis assessment and western blot analyses.

As results, the EtOAc crude extract of mangosteen roots was afforded four new compounds: mangostanone I – IV (compounds 1, 12, 13 and 18) and eighteen known compounds: a-mangostin (2), b-mangostin (3), g-mangostin (4), mangostanaxanthone IV (5), dulxanthone D (6), toxyloxanthone B (7), 1,7-dihydroxy-3-methoxy-2-prenylxanthone (8), euxanthone (9), norathyriol (10), 8-deoxygartanin (11), maclurin (14), 2,3',4,6-tetrahydroxybenzophenone (15), mangaphenone (16), (2-hydroxy-4,6-dimethoxyphenyl)(3-hydroxy-4-methoxyphenyl)methanone (17), garciosine A (19), 4,5-dimethoxy[1,1′-biphenyl]-3-ol (20), 3-hydroxy-4-geranyl-5-methoxybiphenyl (21) and epicatechin (22). It was showed that compound 1, 2, 3, 5, 6, 11 and 21 accommodated potential effects in anticancer properties against investigated cell lines with IC50 less than 50 mM and considerable anti-migration effects against Huh-7. Using Annexin V apoptosis kit, found out that compounds 1, 6 and 11 have an ability to increase apoptosis rate of cell Huh-7 in dose-dependent manner. In addition, western blot analysis revealed that apoptotic activation of 21 in HepG2 was mediated by selective suppression of Bcl-2 expression.