Int J Biol Sci 2019; 15(8):1723-1732. doi:10.7150/ijbs.35284

Research Paper

Ilamycin E, a natural product of marine actinomycete, inhibits triple-negative breast cancer partially through ER stress-CHOP-Bcl-2

Wenhui Zhou1,2,3*, Huan Fang1,2,4*, Qiuju Wu1,2,5*, Xinye Wang2, Rong Liu2,6, Fubin Li2, Ji Xiao2, Lin Yuan5, Zhongmei Zhou2, Junying Ma7, Lulu Wang9, Weiwei Zhao8, Hua You9, Jianhua Ju7, Jing Feng1,8✉, Ceshi Chen2,9,10✉

1. Department of Laboratory Medicine & Central Laboratory, Southern Medical University Affiliated Fengxian Hospital, Shanghai, China, 201499
2. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China, 650223
3. Hubei Key Laboratory of Embryonic Stem Cell Research, Biomedical Research Institute, Hubei University of Medicine, Shiyan, Hubei, China, 442000
4. Fengxian District Center Hospital Graduate Student Training Base, Anhui University of Science & Technology, Shanghai, China, 201499
5. Fengxian District Center Hospital Graduate Student Training Base, Jinzhou Medical University, Shanghai, China, 201499
6. Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China, 650223
7. CAS Key Laboratory of Marine Bio-resources Sustainable Utilization, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China, 510301
8. Shanghai University of Medicine & Health Sciences, Affiliated Sixth People's Hospital South Campus, Shanghai, China, 201499
9. Affiliated Cancer Hospital& Institute of Guangzhou Medical University, Guangzhou, China, 510095
10. KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences
*These authors contributed equally to this work.

Abstract

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women in the worldwide. Triple-negative breast cancer (TNBC) has a poor clinical outcome. The antitumor efficacy of Ilamycins, natural products with anti-tuberculosis activity isolated from deep sea-derived Streptomyces atratus, in TNBC has not been investigated, and the mechanisms remain elusive. Here, we demonstrated that Ilamycin-E, but not -F, decreases cell viability, inhibits G1/S cell cycle progression, and promotes apoptosis in the TNBC cell lines HCC1937 and MDA-MB-468. Ilamycin E promotes apoptosis via activation of endoplasmic reticulum (ER) stress, increasing the expression of CHOP, and down-regulating the expression of anti-apoptotic protein Bcl-2. Depletion of CHOP or overexpression of Bcl2 significantly rescued Ilamycin E-induced apoptosis. These findings indicate that Ilamycin E has anti-cancer activity in TNBC.

Keywords: Ilamycin E, triple-negative breast cancer, ER stress, CHOP, Bcl-2.

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How to cite this article:
Zhou W, Fang H, Wu Q, Wang X, Liu R, Li F, Xiao J, Yuan L, Zhou Z, Ma J, Wang L, Zhao W, You H, Ju J, Feng J, Chen C. Ilamycin E, a natural product of marine actinomycete, inhibits triple-negative breast cancer partially through ER stress-CHOP-Bcl-2. Int J Biol Sci 2019; 15(8):1723-1732. doi:10.7150/ijbs.35284. Available from http://www.ijbs.com/v15p1723.htm