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Updated: Jun 17, 2025

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Bombinin-BO1 induces hepatocellular carcinoma cell-cycle arrest and apoptosis via the HSP90A-Cdc37-CDK1 axis
Xiaoting Wang1,2, Peiyu Tang1,2, Yitong Gong1,3
1Yantai 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.
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.
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