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Mar. Drugs 2018, 16(7), 238; https://doi.org/10.3390/md16070238

A Sterol from Soft Coral Induces Apoptosis and Autophagy in MCF-7 Breast Cancer Cells

1
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
2
Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan
3
Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 40402, Taiwan
4
Cancer Center, China Medical University Hospital, Taichung 40447, Taiwan
5
Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
6
College of Medicine, China Medical University, Taichung 40402, Taiwan
7
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
8
Frontier Center for Ocean Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 20 March 2018 / Revised: 9 July 2018 / Accepted: 11 July 2018 / Published: 17 July 2018
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Abstract

The peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that plays a key role in regulating cellular metabolism, and is a therapeutic target for cancer therapy. To search for potential PPARγ activators, a compound library comprising 11 marine compounds was examined. Among them, a sterol, 3β,11-dihydroxy-9,11-secogorgost-5-en-9-one (compound 1), showed the highest PPARγ activity with an IC50 value of 8.3 μM for inhibiting human breast adenocarcinoma cell (MCF-7) growth. Western blotting experiments showed that compound 1 induces caspase activation and PARP cleavage. In addition, compound 1 modulated the expression of various PPARγ-regulated downstream biomarkers including cyclin D1, cyclin-dependent kinase (CDK)6, B-cell lymphoma 2 (Bcl-2), p38, and extracellular-signal-regulated kinase (ERK). Moreover, compound 1 increased reactive oxygen species (ROS) generation, upregulated the phosphorylation and expression of H2AX, and induced autophagy. Interestingly, pre-treatment with the autophagy inhibitor 3-methyladenine rescued cells from compound 1-induced growth inhibition, which indicates that the cytotoxic effect of compound 1 is, in part, attributable to its ability to induce autophagy. In conclusion, these findings suggest the translational potential of compound 1 in breast cancer therapy. View Full-Text
Keywords: PPARγ; sterol; apoptosis; autophagy; breast cancer PPARγ; sterol; apoptosis; autophagy; breast cancer
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Weng, J.-R.; Chiu, C.-F.; Hu, J.-L.; Feng, C.-H.; Huang, C.-Y.; Bai, L.-Y.; Sheu, J.-H. A Sterol from Soft Coral Induces Apoptosis and Autophagy in MCF-7 Breast Cancer Cells. Mar. Drugs 2018, 16, 238.

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