Selective inhibition of cancer cells by enzyme-induced gain of function of phosphorylated melittin analogues.

Abstract

The selective killing of cancer cells and the avoidance of drug resistance are still difficult challenges in cancer therapy. Here, we report a new strategy that uses enzyme-induced gain of function (EIGF) to regulate the structure and function of phosphorylated melittin analogues (MelAs). Original MelAs have the capacity to disrupt plasma membranes and induce cell death without selectivity. However, phosphorylation of Thr23 on one of the MelAs (MelA2-P) efficiently ameliorated the membrane lysis potency as well as the cytotoxicity for normal mammalian cells. After treatment with alkaline phosphatase (ALP), which is more active in cancer cells than normal cells, MelA2-P restored the pore-forming function around the cancer cells and induced cancer cell death selectively. This mechanism was independent of the receptor proteins and the cell uptake process, which may partially bypass the development of drug resistance in cancer cells.

• Authors: Qian-Qian Li, Pu-Guang Chen, Zhi-Wen Hu, Yuan Cao, Liang-Xiao Chen, Yong-Xiang Chen, Yu-Fen Zhao, Yan-Mei Li
• Journal: Chemical science (Chem Sci) Vol. 8 Issue 11 Pg. 7675-7681 (Nov 01 2017) ISSN: 2041-6520 [Print] England
• PMID: 29568430 (Publication Type: Journal Article)