2. Academic Validation
  3. Repurposing of antipsychotics perphenazine for the treatment of endometrial cancer

Repurposing of antipsychotics perphenazine for the treatment of endometrial cancer

  • Bioorg Med Chem Lett. 2020 Jul 15;30(14):127239. doi: 10.1016/j.bmcl.2020.127239.
Yang Chen 1,  Yunxia Cui 2,  Xiao Sun 2,  Huiwen Wu 1,  Manjiao Ou 1,  Yunzhe Tang 1,  Shuaishuai Ni 3,  Xiaokang Li 1,  Jin Zhu 1,  Fei Mao 4,  Yudong Wang 5,  Jian Li 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
  • 2 Department of Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 3 Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
  • 4 State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. Electronic address: maofei@ecust.edu.cn.
  • 5 Department of Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: owangyudong@126.com.
  • 6 State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. Electronic address: jianli@ecust.edu.cn.
PMID: 32527541 DOI: 10.1016/j.bmcl.2020.127239
Abstract

Endometrial Cancer (EC) is one of the most common and fatal gynecological cancers worldwide, but there is no effective treatment for the EC patients of progesterone resistance. Repurposing of existing drugs is a good strategy to discover new candidate drugs. In this text, perphenazine (PPZ), approved for psychosis therapy, was identified as a potential agent for the treatment of both progesterone sensitive and resistant endometrial Cancer for the first time. Specifically, perphenazine exhibited good cell proliferation inhibition in Ishikawa (ISK) and KLE cell lines according to the CCK-8 assay and colony formation assay. It also reduced the cell migration of ISK and KLE cell lines in the light of the transwell migration assay. Annexin-V/PI double staining assay suggested that perphenazine could effectively induce ISK and KLE cell Apoptosis. Moreover, results of western blot assay indicated perphenazine obviously inhibited the phosphorylation of Akt. Delightedly, PPZ also could significantly attenuate xenograft tumor growth at both 3 mg/kg and 15 mg/kg in mice without influencing the body weights.

Keywords

Endometrial cancer; Medroxyprogesterone acetate; Perphenazine; Progesterone-resistant; Proliferation inhibition.

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