Securinine inhibits the tumor growth of human bladder cancer cells by suppressing Wnt/ β-catenin signaling pathway and activating p38 and JNK signaling pathways

In this study, we evaluated the potential anti-tumor effect of securinine (SEC), a natural alkaloid from Securinega suffruticosa, on BC cells in vitro and in vivo, and delineated the underlying mechanism. We found that SEC inhibited the proliferation, migration and invasion, induced the apoptosis of BC cells in vitro, and retarded the xenograft tumor growth of BC cell in vivo. Notably, SEC had a promising safety profile because it presented no or low toxicity on normal cells and mice. Mechanistically, SEC inactivated Wnt/β-catenin signaling pathway while activated p38 and JNK signaling pathway. Moreover, β-catenin overexpression, the p38 inhibitor SB203580 and the JNK inhibitor SP600125 both mitigated the inhibitory effect of SEC on BC cells. Furthermore, we demonstrated a synergistic inhibitory effect of SEC and gemcitabine (GEM) on BC cells in vitro and in vivo. Taken together, our findings suggest that SEC may exert anti-BC cell effect at least through the activation of p38 and JNK signaling pathways, and the inhibition of Wnt/β-catenin signaling pathway. More meaningfully, the findings indicate that GEM-induced BC cell killing can be enhanced by combining with SEC.PMID:38484850 | DOI:10.1016/j.bcp.2024.116125

Source: Biochemical Pharmacology - March 14, 2024 Category: Drugs & Pharmacology Authors: Liping Xie Shiqiong Liang Habu Jiwa Lulu Zhang Qiuping Lu Xiaoxuan Wang Lijuan Luo Haichao Xia Ziyun Li Jiayu Wang Xiaoji Luo Jinyong Luo Source Type: research