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

• Published in: Journal of cellular biochemistry Vol. 121; no. 1; pp. 81 - 92
• Main Authors: Tan, Hailin, Zhang, Guiming, Yang, Xuecheng, Jing, Tao, Shen, Daqing, Wang, Xinsheng
• Format: Journal Article
• Language: English
• Published: United States 01.01.2020
• Subjects: Animals; Anthracenes - pharmacology; Apoptosis; Calcium - metabolism; Calcium Signaling; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Cell Line, Tumor; Cell Movement; Cell Survival; Cevanes - pharmacology; Fritillaria - chemistry; Homeostasis - drug effects; Humans; Male; MAP Kinase Kinase 4 - metabolism; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasm Transplantation; Phosphorylation; Prostatic Neoplasms - metabolism; Wound Healing; peimine; prostate cancer; calcium; JNK; endoplasmic reticulum stress; Ca2+/CaMKII
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28870

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 ) 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 concentration, the increased Ca promoted the phosphorylation of Ca /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 chelator BAPTA-AM (1 μM) could counteract the increase of intracellular Ca 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 /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 /CaMKII/JNK pathway.