Inhibitory effects of docosyl p-coumarate on DNA topoisomerase activity and human cancer cell growth

  • Authors:
    • Yoshiyuki Mizushina
    • Katsumi Nishimura
    • Yukiko Takenaka
    • Toshifumi Takeuchi
    • Fumio Sugawara
    • Hiromi Yoshida
    • Takao Tanahashi
  • View Affiliations

  • Published online on: October 1, 2010     https://doi.org/10.3892/ijo_00000750
  • Pages: 993-1000
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Abstract

We previously found six compounds of alkyl p-coumarates from a composite plant Artemisia annua L., and chemically synthesized these compounds (cis-isomer of C20, C22 and C24, and trans-isomer of C20, C22 and C24 of p-coumarates are compounds 1-6, respectively). This report describes the inhibitory activities of these alkyl p-coumarates against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compounds 1 and 4 weakly inhibited repair-related pol β activity, but no compound influenced the activity of replicative pol α. Compounds 4-6 and compounds 2 and 5 were potent inhibitors of human topos I and II, respectively. Compounds 2, 4, 5 and 6 also suppressed the growth of human colon carcinoma cell line, HCT116, with or without p53, suggesting that cell growth inhibition had the same tendency as the inhibition of topos rather than pols. Compound 5 (docosyl p-coumarate), which was the strongest inhibitor of topo II and cancer cell growth in the compounds tested, halted HCT116 p53+/+ cells in G2/M phases, and induced apoptosis, although this compound did not affect the cell cycle of HCT116 p53−/− cells. These results suggest that the effect of p53-dependent cell cycle arrest may be effective for topo inhibition by com-pound 5. From these findings, the action mode of alkyl p-coumarates as an anti-cancer agent is discussed.

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October 2010
Volume 37 Issue 4

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

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Spandidos Publications style
Mizushina Y, Nishimura K, Takenaka Y, Takeuchi T, Sugawara F, Yoshida H and Tanahashi T: Inhibitory effects of docosyl p-coumarate on DNA topoisomerase activity and human cancer cell growth. Int J Oncol 37: 993-1000, 2010.
APA
Mizushina, Y., Nishimura, K., Takenaka, Y., Takeuchi, T., Sugawara, F., Yoshida, H., & Tanahashi, T. (2010). Inhibitory effects of docosyl p-coumarate on DNA topoisomerase activity and human cancer cell growth. International Journal of Oncology, 37, 993-1000. https://doi.org/10.3892/ijo_00000750
MLA
Mizushina, Y., Nishimura, K., Takenaka, Y., Takeuchi, T., Sugawara, F., Yoshida, H., Tanahashi, T."Inhibitory effects of docosyl p-coumarate on DNA topoisomerase activity and human cancer cell growth". International Journal of Oncology 37.4 (2010): 993-1000.
Chicago
Mizushina, Y., Nishimura, K., Takenaka, Y., Takeuchi, T., Sugawara, F., Yoshida, H., Tanahashi, T."Inhibitory effects of docosyl p-coumarate on DNA topoisomerase activity and human cancer cell growth". International Journal of Oncology 37, no. 4 (2010): 993-1000. https://doi.org/10.3892/ijo_00000750