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Article

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
  • View Affiliations / Copyright

    Affiliations: Cooperative Research Center of Life Sciences, Kobe Gakuin University, Chuo-ku, Kobe, Hyogo 651-8586, Japan, Kobe Pharmaceutical University, Higashinada-ku, Kobe, Hyogo 658-8558, Japan, Graduate School of Agriculture, Shinshu University, Minamiminowa-mura, Kamiina-gun, Nagano 399-4598, Japan
  • Pages: 1145-1154
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    Published online on: January 5, 2016
       https://doi.org/10.3892/ijo.2016.3321
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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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Copy and paste a formatted citation
Spandidos Publications style
Onodera T, Takenaka Y, Kozaki S, Tanahashi T and Mizushina Y: Screening of mammalian DNA polymerase and topoisomerase inhibitors from Garcinia mangostana L. and analysis of human cancer cell proliferation and apoptosis. Int J Oncol 48: 1145-1154, 2016.
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
Copy and paste a formatted citation
x
Spandidos Publications style
Onodera T, Takenaka Y, Kozaki S, Tanahashi T and Mizushina Y: Screening of mammalian DNA polymerase and topoisomerase inhibitors from Garcinia mangostana L. and analysis of human cancer cell proliferation and apoptosis. Int J Oncol 48: 1145-1154, 2016.
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
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