Screening of mammalian DNA polymerase and topoisomerase inhibitors from Garcinia mangostana L. and analysis of human cancer cell proliferation and apoptosis.

We purified and identified eight xanthones from mangosteen (Garcinia mangostana L.) and investigated whether these compounds inhibited the activities of mammalian DNA polymerases (Pols) and human DNA topoisomerases (Topos). ß-Mangostin was the strongest inhibitor of both mammalian Pols and human Topos among the isolated xanthones, with 50% inhibitory concentration (IC50) values of 6.4-39.6 and 8.5-10 µM, respectively. Thermal transition analysis indicated that ß-mangostin did not directly bind to double-stranded DNA, suggesting that this compound directly bound the enzyme protein rather than the DNA substrate. ß-Mangostin showed the strongest suppression of human cervical cancer HeLa cell proliferation among the eight compounds tested, with a 50% lethal dose (LD50) of 27.2 µM. This compound halted cell cycle in S phase at 12-h treatment and induced apoptosis. These results suggest that decreased proliferation by ß-mangostin may be a result of the inhibition of cellular Pols rather than Topos, and ß-mangostin might be an anticancer chemotherapeutic agent.

Three acetophenones from Acronychia pedunculata.

Phytochemical investigation of the leaves and twigs of Acronychia pedunculata has led to the isolation of three new acetophenone monomers 1-3 as well as 1-[2',4'-dihydroxy-3',5'-di-(3″-methyl-2″-butenyl)-6'-methoxy]phenylethanone (4), acronyculatin E (5), a mixture of ß-sitosterol and stigmasterol, and sesamin. The structures of these new compounds were elucidated spectroscopically. The inhibitory activities of the isolated acetophenone derivatives against mammalian DNA polymerases and human cancer cell growth were also assessed.