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Peimine inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca 2+ /CaMKII/JNK pathway
Author(s) -
Tan Hailin,
Zhang Guiming,
Yang Xuecheng,
Jing Tao,
Shen Daqing,
Wang Xinsheng
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28870
Subject(s) - lncap , apoptosis , intracellular , bapta , motility , kinase , cell growth , chemistry , cancer cell , calcium in biology , microbiology and biotechnology , calmodulin , protein kinase a , calcium , biology , medicine , cancer , biochemistry , organic chemistry
Abstract Prostate cancer (PC) is one of the most common malignant tumors in man. Peimine (PM) is a bioactive substance isolated from Fritillaria . Previous studies have shown that PM could inhibit the occurrence of a variety of cancers. However, the roles of PM in PC and its related mechanism have not been elucidated. Calcium (Ca 2+ ) is an important intracellular messenger involved in a variety of cell processes. In this study, we found that the appropriate doses of PM (2.5, 5, and 10 μM) significantly inhibited the growth of PC cells (DU‐145, LNCap, and PC‐3), but has no significant effect on normal prostate cells (RWPE‐1). In addition, PM treatment inhibited the invasion and migration of PC‐3 cells and blocked the epithelial‐mesenchymal transition process. These effects were exhibited a dose‐dependent manner. Furthermore, the current results also showed that PM treatment significantly increased the Ca 2+ concentration, the increased Ca 2+ promoted the phosphorylation of Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII) and c‐Jun N‐terminal kinase (JNK), further inhibited the growth and invasion of PC‐3 cells, and induced its apoptosis. Ca 2+ chelator BAPTA‐AM (1 μM) could counteract the increase of intracellular Ca 2+ concentration. Similarly, JNK pathway inhibitor SP600125 (10 μM) also inhibited cell growth and invasion and induced apoptosis. In addition, experiments in nude mice showed that PM inhibited tumor formation through Ca 2+ /CaMKII/JNK signaling pathway. In conclusion, our results show that PM inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca 2+ /CaMKII/JNK pathway.