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

Kanno,Syu-Ichi; Yomogida,Shin; Tomizawa,Ayako; Yamazaki,Hiroyuki; Ukai,Kazuyo; Mangindaan,Remy   E.P.; Namikoshi,Michio; Ishikawa,Masaaki

doi:10.3892/ijo.2013.2093

November 2013 Volume 43 Issue 5

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November 2013 Volume 43 Issue 5

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Article 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 / Copyright

Affiliations: Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan, Department of Natural Product Chemistry, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan, Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia

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

https://doi.org/10.3892/ijo.2013.2093
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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.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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