Open Access

Papuamine causes autophagy following the reduction of cell survival through mitochondrial damage and JNK activation in MCF-7 human breast cancer cells

  • Authors:
    • Syu-Ichi Kanno
    • Shin Yomogida
    • Ayako Tomizawa
    • Hiroyuki Yamazaki
    • Kazuyo Ukai
    • Remy E.P. Mangindaan
    • Michio Namikoshi
    • Masaaki Ishikawa
  • View Affiliations

  • Published online on: September 10, 2013     https://doi.org/10.3892/ijo.2013.2093
  • Pages: 1413-1419
  • Copyright: © Kanno et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

We previously reported that extracts of an Indonesian marine sponge Haliclona sp. showed potent cytotoxicity and the induction of apoptosis against human solid cancer cell lines. In this study, we examine the cytotoxic mechanism of the major chemical compound, papuamine, on MCF-7 human breast cancer cells. Papuamine at 5 µM did not show significant cytotoxic effects after incubation for 24 h, but autophagosome vesicular formation was apparent. At 10 µM of papuamine, significant reduction in cell survival was observed at 12 h, and increases in autophagy at this concentration were time-dependent and apparent before the appearance of cytotoxic effects. Both the release of cytochrome c to the cytosol and increase in Bax in the mitochondrial fraction were found to be concentration-dependent. Moreover, mitochondrial membrane potential shows concentration- and time-dependent decreases with exposure to papuamine. The release of cytochrome c has been shown to be accompanied by an increase in JNK activation. 3-Methyladenine (MA), a classical autophagy inhibitor showed increased JNK activation by exposure to papuamine. In conclusion, our results indicate that papuamine causes earlier onset autophagy and delayed reduction of cell survival through mitochondrial damage and JNK activation in MCF-7 cells.

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November 2013
Volume 43 Issue 5

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

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Copy and paste a formatted citation
APA
Kanno, S., Yomogida, S., Tomizawa, A., Yamazaki, H., Ukai, K., Mangindaan, R.E. ... Ishikawa, M. (2013). Papuamine causes autophagy following the reduction of cell survival through mitochondrial damage and JNK activation in MCF-7 human breast cancer cells. International Journal of Oncology, 43, 1413-1419. https://doi.org/10.3892/ijo.2013.2093
MLA
Kanno, S., Yomogida, S., Tomizawa, A., Yamazaki, H., Ukai, K., Mangindaan, R. E., Namikoshi, M., Ishikawa, M."Papuamine causes autophagy following the reduction of cell survival through mitochondrial damage and JNK activation in MCF-7 human breast cancer cells". International Journal of Oncology 43.5 (2013): 1413-1419.
Chicago
Kanno, S., Yomogida, S., Tomizawa, A., Yamazaki, H., Ukai, K., Mangindaan, R. E., Namikoshi, M., Ishikawa, M."Papuamine causes autophagy following the reduction of cell survival through mitochondrial damage and JNK activation in MCF-7 human breast cancer cells". International Journal of Oncology 43, no. 5 (2013): 1413-1419. https://doi.org/10.3892/ijo.2013.2093