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Food Chem Toxicol. 2013 Sep;59:793-800. doi: 10.1016/j.fct.2013.06.027. Epub 2013 Jun 26.

Inhibitory effects of α-mangostin on mammalian DNA polymerase, topoisomerase, and human cancer cell proliferation.

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1
Laboratory of Food & Nutritional Sciences, Faculty of Nutrition, Kobe Gakuin University, Nishi-ku, Kobe, Hyogo, Japan. mizushin@nutr.kobegakuin.ac.jp

Abstract

We found that the ethanol extract of mangosteen (Garcinia mangostana L.) fruit rind had a strong inhibitory effect on mammalian DNA polymerase (pol) activity and isolated α-mangostin as a potent pol inhibitor from the extract. In this study, the inhibitory activities against mammalian pols by α-mangostin and its related five compounds, 3-isomangostin, xanthone, 9,10-anthraquinone, 9-anthracenecarboxylic acid, and anthracene, were investigated. α-Mangostin was the most potent inhibitor of the mammalian pol species among the tested compounds, with IC₅₀ values of 14.8-25.6 μM. This compound also inhibited human DNA topoisomerases (topos) I and II activities with IC₅₀ values of 15.0 and 7.5 μM, respectively, but did not inhibit the activities of other DNA metabolic enzymes tested. α-Mangostin also did not directly bind to double-stranded DNA as determined by thermal transition analysis. α-Mangostin was found to suppress human colon HCT116 carcinoma cell proliferation with an LC₅₀ of 18.5 μM, inhibit the activity of cellular topos, halt cell cycle in the G2/M phase, and induce apoptosis. These results suggest that decreased proliferation by α-mangostin may be a result of the inhibition of cellular topos rather than pols, and α-mangostin might be an anticancer chemotherapeutic agent.

KEYWORDS:

Anticancer foods; DNA polymerase inhibition; DNA topoisomerase inhibition; Mangosteen; α-Mangostin

PMID:
23811100
DOI:
10.1016/j.fct.2013.06.027
[Indexed for MEDLINE]
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