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

  • Authors:
    • Takefumi Onodera
    • Yukiko Takenaka
    • Sachiko Kozaki
    • Takao Tanahashi
    • Yoshiyuki Mizushina
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  • Published online on: January 5, 2016     https://doi.org/10.3892/ijo.2016.3321
  • Pages: 1145-1154
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Abstract

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). β-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 β-mangostin did not directly bind to double-stranded DNA, suggesting that this compound directly bound the enzyme protein rather than the DNA substrate. β-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 β-mangostin may be a result of the inhibition of cellular Pols rather than Topos, and β-mangostin might be an anticancer chemotherapeutic agent.
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March 2016
Volume 48 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Onodera, T., Takenaka, Y., Kozaki, S., Tanahashi, T., & Mizushina, Y. (2016). Screening of mammalian DNA polymerase and topoisomerase inhibitors from Garcinia mangostana L. and analysis of human cancer cell proliferation and apoptosis. International Journal of Oncology, 48, 1145-1154. https://doi.org/10.3892/ijo.2016.3321
MLA
Onodera, T., Takenaka, Y., Kozaki, S., Tanahashi, T., Mizushina, Y."Screening of mammalian DNA polymerase and topoisomerase inhibitors from Garcinia mangostana L. and analysis of human cancer cell proliferation and apoptosis". International Journal of Oncology 48.3 (2016): 1145-1154.
Chicago
Onodera, T., Takenaka, Y., Kozaki, S., Tanahashi, T., Mizushina, Y."Screening of mammalian DNA polymerase and topoisomerase inhibitors from Garcinia mangostana L. and analysis of human cancer cell proliferation and apoptosis". International Journal of Oncology 48, no. 3 (2016): 1145-1154. https://doi.org/10.3892/ijo.2016.3321