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Mar. Drugs 2018, 16(4), 104; https://doi.org/10.3390/md16040104

7-Acetylsinumaximol B Induces Apoptosis and Autophagy in Human Gastric Carcinoma Cells through Mitochondria Dysfunction and Activation of the PERK/eIF2α/ATF4/CHOP Signaling Pathway

1
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
2
Department of Nephrology, Antai Medical Care Corporation Antai Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan
3
National Museum of Marine Biology & Aquarium, Pingtung 94450, Taiwan
4
Department of Biological Technology, Mei-ho University, Pingtung 91202, Taiwan
5
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
6
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
7
Frontier Center for Ocean Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
8
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 16 January 2018 / Revised: 18 March 2018 / Accepted: 22 March 2018 / Published: 26 March 2018
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Abstract

The 7-Acetylsinumaximol B (7-AB), a bioactive cembranoid, was originally discovered from aquaculture soft coral Sinularia sandensis. The current study investigated the anti-proliferative property of 7-AB towards the NCI-N87 human gastric cancer cell line. An MTT cell proliferative assay was applied to evaluate cell survival, and immunofluorescence staining and western blotting were employed to analyze the effects of 7-AB on autophagy and apoptosis. Our results showed that 7-AB exerted a concentration-dependent anti-proliferative effect on NCI-N87 cells, and fluorescence staining indicated that the effect was due to the apoptosis induced by 7-AB. In addition, the 7-AB-induced anti-proliferation towards NCI-N87 cells was associated with the release of cytochrome c from mitochondria, activation of pro-apoptotic proteins (such as caspase-3/-9, Bax and Bad), and inhibition of anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1). The 7-AB treatment also triggered endoplasmic reticulum (ER) stress, leading to activation of the PERK/elF2α/ATF4/CHOP apoptotic pathway. Furthermore, 7-AB initiated autophagy in NCI-N87 cells and induced the expression of autophagy-related proteins, including Atg3, Atg5, Atg7, Atg12, LC3-I, and LC3-II. Taken together, our findings suggested that 7-AB has the potential to be further developed as a useful anti-cancer or adjuvant agent for the treatment of human gastric cancer. View Full-Text
Keywords: 7-acetylsinumaximol B; human gastric cancer cells; endoplasmic reticulum stress; mitochondrial inactivation; autophagy 7-acetylsinumaximol B; human gastric cancer cells; endoplasmic reticulum stress; mitochondrial inactivation; autophagy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Tsai, T.-C.; Lai, K.-H.; Su, J.-H.; Wu, Y.-J.; Sheu, J.-H. 7-Acetylsinumaximol B Induces Apoptosis and Autophagy in Human Gastric Carcinoma Cells through Mitochondria Dysfunction and Activation of the PERK/eIF2α/ATF4/CHOP Signaling Pathway. Mar. Drugs 2018, 16, 104.

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