Wang Xiaoting, Tang Peiyu, Gong Yitong, Yao Hang, Liang Mingpeng, Qu Hongxia, Han Xiao, Zheng Qiusheng, Shi Zhen, Li Defang, Jiang Qingling
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.
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.
iScience. 2024 Jun 26;27(8):110382. doi: 10.1016/j.isci.2024.110382. eCollection 2024 Aug 16.
Bombinin-BO1 (BO1), a bombinin peptide derived from the skin secretion of , 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. , 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.
蛙皮素-BO1（BO1）是一种源自蛙皮分泌物的蛙皮素肽，具有广谱抗菌活性。迄今为止，BO1的抗癌作用仍不清楚。本研究通过诱导S期周期阻滞和细胞凋亡证实了BO1对肝癌细胞的细胞毒性。此外，发现BO1通过内吞作用定位于细胞质中。下拉实验、质谱分析和免疫共沉淀的综合结果表明，BO1通过与Cdc37竞争性结合HSP90A诱导CDK1错误折叠并降解。证实BO1处理细胞中HSP90A的过表达显著抑制了CDK1的降解。此外，BO1抑制肿瘤且对个体无毒。本研究揭示了BO1通过干扰HSP90A-Cdc37-CDK1系统诱导细胞周期阻滞和细胞凋亡的抗肿瘤机制。这是第一项分析BO1调节肿瘤细胞机制的研究，为BO1治疗肝癌提供了理论依据。
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