A Novel Polypeptide Extracted From Ciona savignyi Induces Apoptosis Through a Mitochondrial-Mediated Pathway in Human Colorectal Carcinoma Cells

作者：Cheng Linyou; Wang Chunguang; Liu Haizhou; Wang Fengxia; Zheng Lanhong; Zhao Jin; Chu Edward; Lin Xiukun^*

来源：Clinical Colorectal Cancer, 2012, 11(3): 207-214.

DOI：10.1016/j.dcc.2012.01.002

• Antitumor
• Ciona savignyi
• Polypeptide
• Purification and identification

An ascidian is a marine animal that is important in the pharmacology field. Many compounds with special bioactivity, especially those with antitumor properties, have been developed from it. We extracted and purified a novel polypeptide with potent antitumor activity from the Ciona savignyi (an ascidian) by chromatography. Our results suggest that the polypeptide is a promising drug candidate for the treatment of cancer.
Background: Sessile marine animals such as sponges, ascidians, and bryozoans are a rich source of bioactive natural products, many of which exhibit potent anticancer activity. Materials and Methods: We extracted and purified a polypeptide with potent antitumor activity from Ciona savignyi by acetone fractionation, ultrafiltration, ion exchange chromatography, gel chromatography, and high-performance liquid chromatography. An MTT assay was used to study the cytotoxicity of the isolated fraction and the purified polypeptide. Cell cycle and Western blot analysis were performed to study the mode of action of the purified polypeptide. Results: A novel polypeptide with potent antitumor activity was purified. The molecular weight of the polypeptide, designated CS5931, was 5931 Da, and use of the genome basic local alignment search tool (BLAST) revealed that the N-terminal sequence of CS5931 is identical to that of granulin A from C savignyi. CS5931 exhibited significant cytotoxicity for several cancer cell types and induced apoptotic death in HCT-8 cells in a dose- and time-dependent manner. Cell cycle analysis demonstrated that CS5931 caused cell cycle arrest at the G(2)/M phase, and a sub-G(1) peak appeared after treating the cells with CS5931 for 12 hours. The mitochondrial-mediated pathway was implicated in CS5931-induced apoptosis. Conclusion: Our observations clearly demonstrate the antiproliferative and proapoptotic activities of the polypeptide CS5931 from C savignyi and the mitochondrial-mediated pathway involved in the polypeptide-induced cell death.

• 出版日期2012-9
• 单位同济大学; 中国科学院海洋研究所