文献类型：期刊文献

英文题名：Effectively enhancing cytotoxic and apoptotic effects of alpha-momorcharin by integrating a heparin-binding peptide

作者：Tan, Meng-Jie[1];Cao, Xue-Wei[1];Li, Peng-Fei[1];Zhai, Yi-Zhou[1];Zhou, Yu[1];Liu, Ye-Jun[1];Zhao, Jian[1];Wang, Fu-Jun[2,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Zhejiang Reachall Pharmaceut Co Ltd, Hangzhou, Zhejiang, Peoples R China;[3]Shanghai Univ Chinese Tradit Med, Inst Chinese Mat Med, 1200 Cailun Rd, Shanghai 201203, Peoples R China

年份：2017

卷号：64

期号：6

起止页码：918

外文期刊名：BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY

收录：;EI(收录号：20171703613034);WOS:【SCI-EXPANDED(收录号:WOS:000418111300017)】；

基金：This work was supported by the National Natural Science Foundation of China (Grant No. 81571795). The authors declare no conflict of interest.

语种：英文

外文关键词：antitumor activity; apoptosis; cell-penetrating peptides; heparin-binding peptide; alpha-MMC-HBP

摘要：Alpha-momorcharin (-MMC), a type I ribosome-inactivating protein, has attracted a great deal of attention because of its antitumor activity. However, the cytotoxicity of -MMC is limited due to insufficient cellular internalization in cancer cells. To enhance the cytotoxicity of -MMC, a heparin-binding domain derived from heparin-binding epidermal growth factor (named heparin-binding peptide [HBP]) was used as a cell-penetrating peptide and fused to the C-terminus of -MMC. This novel -MMC-HBP fusion protein was expressed and purified with a Ni2+-resin. The N-glycosidase activity and DNase activity assay indicated that the introduction of HBP did not interfere with the intrinsic bioactivities of -MMC. HBP was able to efficiently carry -MMC into the tested cancer cells and significantly enhance the cytotoxic effects of -MMC in a dose-dependent manner. This enhanced cytotoxic ability occurred due to the higher level of cell apoptosis induced by -MMC-HBP, which was demonstrated in western blot analysis in which -MMC-HBP triggered caspase 8, caspase 9, casapase 3, and PARP more intensely than -MMC alone. -MMC-HBP led to an upregulation of cleaved PARP and an increase in the Bax/Bcl-2 ratio. Our study provided a new practical way to greatly improve the antitumor activity of -MMC, which could significantly expand the pharmaceutical applications of alpha-MMC. (C) 2017 International Union of Biochemistry and Molecular Biology, Inc.