Selective inhibition of cancer cells by enzyme-induced gain of function of phosphorylated melittin analogues
| Autor: | Yuan Cao, Zhi-Wen Hu, Liang-Xiao Chen, Pu-Guang Chen, Yufen Zhao, Yan-Mei Li, Yong-Xiang Chen, Qian-Qian Li |
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| Rok vydání: | 2017 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Programmed cell death Cell Biology 010402 general chemistry 01 natural sciences Melittin 03 medical and health sciences chemistry.chemical_compound stomatognathic system medicine Cytotoxicity Receptor musculoskeletal neural and ocular physiology General Chemistry musculoskeletal system 0104 chemical sciences Cell biology Chemistry 030104 developmental biology medicine.anatomical_structure chemistry Cancer cell Phosphorylation Alkaline phosphatase |
| Zdroj: | Chemical Science |
| ISSN: | 2041-6539 2041-6520 |
| Popis: | Developing an enzyme-induced gain of function strategy to selectively kill cancer cells with high ALP activity. 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. |
| Databáze: | OpenAIRE |
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