Int J Biol Sci 2021; 17(13):3493-3507. doi:10.7150/ijbs.62339 This issue

Research Paper

Discovery of a novel HDACi structure that inhibits the proliferation of ovarian cancer cells in vivo and in vitro

Miao Bai1#, Mengqi Cui1#, Mingyue Li1, Xinlei Yao1, Yulun Wu1, Lihua Zheng2, Luguo Sun1, Qiuhang Song3, Shuyue Wang1, Lei Liu1, Chunlei Yu2, Yanxin Huang1✉

1. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China.
2. Research Center of Agriculture and Medicine gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 130024, China.
3. Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang, China.
#These authors contributed equally to this work.

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Citation:
Bai M, Cui M, Li M, Yao X, Wu Y, Zheng L, Sun L, Song Q, Wang S, Liu L, Yu C, Huang Y. Discovery of a novel HDACi structure that inhibits the proliferation of ovarian cancer cells in vivo and in vitro. Int J Biol Sci 2021; 17(13):3493-3507. doi:10.7150/ijbs.62339. Available from https://www.ijbs.com/v17p3493.htm

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Abstract

Graphic abstract

Histone deacetylases (HDACs) exhibit increased expression in cancer and promote oncogenesis via the acetylation of or interactions with key transcriptional regulators. HDAC inhibitors (HDACis) decrease HDAC activity to selectively inhibit the occurrence and development of tumors. Our study screened and obtained a new HDACi structure. In vitro experiments have showed that among the leads, Z31216525 significantly inhibited the proliferation and induced the apoptosis of epithelial ovarian cancer (EOC) cells. In vivo experiments demonstrated that compared to the control, Z31216525 significantly inhibited tumor growth and showed very low toxicity. Further mechanistic studies revealed that Z31216525 may exert an antitumor effect by inhibiting the expression of the c-Myc gene. Collectively, our studies identified a novel HDACi that is expected to become a new potential therapeutic drug for EOC and has important value for the design of new HDACi structures.

Keywords: HDACi, EOC, c-Myc, HDAC7