Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 59, Issue -, Pages 793-800Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2013.06.027
Keywords
alpha-Mangostin; Mangosteen; DNA polymerase inhibition; DNA topoisomerase inhibition; Anticancer foods
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Funding
- MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan)
- MEXT [24580205, 23710262]
- Hyogo Science and Technology Association (Japan)
- Grants-in-Aid for Scientific Research [23710262, 24580205] Funding Source: KAKEN
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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 alpha-mangostin as a potent pol inhibitor from the extract. In this study, the inhibitory activities against mammalian pols by alpha-mangostin and its related five compounds, 3-isomangostin, xanthone, 9,10-anthraquinone, 9-anthracenecarboxylic acid, and anthracene, were investigated. alpha-Mangostin was the most potent inhibitor of the mammalian pol species among the tested compounds, with IC50 values of 14.8-25.6 mu M. This compound also inhibited human DNA topoisomerases (topos) I and II activities with IC50 values of 15.0 and 7.5 mu M, respectively, but did not inhibit the activities of other DNA metabolic enzymes tested. alpha-Mangostin also did not directly bind to double-stranded DNA as determined by thermal transition analysis. alpha-Mangostin was found to suppress human colon HCT116 carcinoma cell proliferation with an LC50 of 18.5 mu M, inhibit the activity of cellular topos, halt cell cycle in the G2/M phase, and induce apoptosis. These results suggest that decreased proliferation by alpha-mangostin may be a result of the inhibition of cellular topos rather than pols, and alpha-mangostin might be an anticancer chemotherapeutic agent. (C) 2013 Elsevier Ltd. All rights reserved.
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