2. Academic Validation
  3. Pharmacological USP2 targeting suppresses ovarian cancer growth by potentiating apoptosis and ferroptosis

Pharmacological USP2 targeting suppresses ovarian cancer growth by potentiating apoptosis and ferroptosis

  • Arch Biochem Biophys. 2024 Dec:762:110193. doi: 10.1016/j.abb.2024.110193.
Dian Yang 1,  Xiuxiu Liu 2,  Yinghui Yang 1,  Yu Long 1,  Ding Nan 1,  Bo Shi 1,  Jinhao Wang 1,  Mei Yang 1,  Haotian Cong 1,  Lin Xing 1,  Feixue Zhou 1,  Qianhui Yuan 1,  Na Ta 1,  Yingqiu Zhang 1,  Ruilan Ma 3,  Fang Liu 4,  Shuyan Liu 5
Affiliations

Affiliations

  • 1 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
  • 2 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; Department of Gynecology, Zhongshan Hospital of Dalian University, Dalian, China.
  • 3 Department of Radiation Oncology, The Second Affiliated Hospital, Dalian Medical University, China. Electronic address: maruilan2000@163.com.
  • 4 Department of Oncology, The Second Affiliated Hospital, Dalian Medical University, China. Electronic address: liufang_dy@sina.com.
  • 5 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. Electronic address: liusy@dmu.edu.cn.
PMID: 39486565 DOI: 10.1016/j.abb.2024.110193
Abstract

Ovarian Cancer is a frequently observed type of gynaecologic malignancy generally associated with poor prognosis around the world. Ubiquitin-specific proteases (USPs) form the largest subfamily of deubiquitylating Enzymes and have emerged as potential therapeutic targets against human cancers. Through a systematic analysis of the prognostic significance of USP expression, USP2 was found to be inversely correlated with patient survival in ovarian Cancer. Accordingly, we investigated the effects of pharmacological inhibition of USP2 on ovarian Cancer by exploiting its small molecule inhibitor ML364. Our findings show that ML364 effectively hindered ovarian Cancer growth and migration using a series of in vitro assays. In addition to Apoptosis induction, ML364 also sensitized ovarian Cancer cells to Ferroptosis. Mechanistically, ML364 treatment resulted in cyclin D1 downregulation, increased poly (ADP-ribose) polymerase (PARP) cleavage, and elevated ROS levels in ovarian Cancer cells. Collectively, our findings suggest USP2 as a potential therapeutic target in ovarian Cancer, and hence, its pharmacological inhibition warrants further investigation.

Keywords

Apoptosis; Ferroptosis; ML364; Ovarian cancer; USP2.

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