Pyranicin, a non-classical annonaceous acetogenin, is a potent inhibitor of DNA polymerase, topoisomerase and human cancer cell growth

  • Authors:
    • Shunya Takahashi
    • Yuko Yonezawa
    • Akemi Kubota
    • Narihito Ogawa
    • Katsuya Maeda
    • Hiroyuki Koshino
    • Tadashi Nakata
    • Hiromi Yoshida
    • Yoshiyuki Mizushina
  • View Affiliations

  • Published online on: February 1, 2008     https://doi.org/10.3892/ijo.32.2.451
  • Pages: 451-458
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Abstract

This report describes the inhibitory activities of the natural and non-natural acetogenins [mucocin (compound 1), jimenezin (compound 2), 19-epi jimenezin (compound 3), muconin (compound 4), pyranicin (compound 5), pyragonicin (compound 6), 10-epi pyragonicin (compound 7), and a γ-lactone (compound 8)], which were synthesized by us, against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compound 5 was revealed to be the strongest inhibitor of the animal pols and human topos tested, and the IC50 values for pols and topos were 2.3-15.8 and 5.0-7.5 µM, respectively. The compound also suppressed human cancer cell (promyelocytic leukemia cell line, HL-60) growth with the same tendency as the inhibition of pols and topos and the LD50 value was 9.4 µM. Compound 5 arrested the cells at G2/M and G1 phases, and prevented the incorporation of thymidine into the cells, indicating that it blocks DNA replication by inhibiting the activity of pols and topos. This compound also induced apoptosis of the cells. Based on these results, the action mode of compound 5 is discussed.

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February 2008
Volume 32 Issue 2

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

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Spandidos Publications style
Takahashi S, Yonezawa Y, Kubota A, Ogawa N, Maeda K, Koshino H, Nakata T, Yoshida H and Mizushina Y: Pyranicin, a non-classical annonaceous acetogenin, is a potent inhibitor of DNA polymerase, topoisomerase and human cancer cell growth. Int J Oncol 32: 451-458, 2008.
APA
Takahashi, S., Yonezawa, Y., Kubota, A., Ogawa, N., Maeda, K., Koshino, H. ... Mizushina, Y. (2008). Pyranicin, a non-classical annonaceous acetogenin, is a potent inhibitor of DNA polymerase, topoisomerase and human cancer cell growth. International Journal of Oncology, 32, 451-458. https://doi.org/10.3892/ijo.32.2.451
MLA
Takahashi, S., Yonezawa, Y., Kubota, A., Ogawa, N., Maeda, K., Koshino, H., Nakata, T., Yoshida, H., Mizushina, Y."Pyranicin, a non-classical annonaceous acetogenin, is a potent inhibitor of DNA polymerase, topoisomerase and human cancer cell growth". International Journal of Oncology 32.2 (2008): 451-458.
Chicago
Takahashi, S., Yonezawa, Y., Kubota, A., Ogawa, N., Maeda, K., Koshino, H., Nakata, T., Yoshida, H., Mizushina, Y."Pyranicin, a non-classical annonaceous acetogenin, is a potent inhibitor of DNA polymerase, topoisomerase and human cancer cell growth". International Journal of Oncology 32, no. 2 (2008): 451-458. https://doi.org/10.3892/ijo.32.2.451