Bombinin-BO1 induces hepatocellular carcinoma cell-cycle arrest and apoptosis via the HSP90A-Cdc37-CDK1 axis

  • iScience. 2024 Jun 26;27(8):110382. doi: 10.1016/j.isci.2024.110382.
Xiaoting Wang  1  2 ,  Peiyu Tang  1  2 ,  Yitong Gong  1  3 ,  Hang Yao  1  2 ,  Mingpeng Liang  1  2 ,  Hongxia Qu  1  2 ,  Xiao Han  1  2 ,  Qiusheng Zheng  1  2 ,  Zhen Shi  3 ,  Defang Li  1  2 ,  Qingling Jiang  1  2
Affiliations
  • 1. Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
  • 2. Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
  • 3. School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003, Shandong, P.R. China.
PMID: 39108730 DOI: 10.1016/j.isci.2024.110382
Abstract

Bombinin-BO1 (BO1), a bombinin peptide derived from the skin secretion of Bombina orientalis, exhibits broad-spectrum antimicrobial activity. To date, the Anticancer effect of BO1 remains unclear. This study confirmed cytotoxicity of BO1 on hepatocellular carcinoma cells by inducing S-phase cycle block and Apoptosis. In addition, BO1 was found to be localized in cytoplasm through endocytosis. The combined results of pull down, mass spectrometry, and co-immunoprecipitation suggested that BO1 induced misfolding of CDK1 and degradation by competitively binding HSP90A with Cdc37. It was verified that overexpression of HSP90A in BO1-treated cells significantly inhibited degradation of CDK1. In vivo, BO1 inhibited tumor without being toxic to individuals. This study reveals the anti-tumor mechanism of BO1 in inducing cell-cycle arrest and Apoptosis by interfering with HSP90A-Cdc37-CDK1 system. This is the first study to analyze the mechanism of BO1 regulation of tumor cells, providing theoretical basis for BO1 treatment of hepatocellular carcinoma.

Keywords
Biological sciences; Cancer; System biology.
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