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

• DOI: 10.1016/j.bcp.2024.116125
• Publication Date: 2024-03-12T17:04:22Z
• 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
• Keywords: MAP Kinase Signaling System; Antineoplastic Agents; Apoptosis; Azepines; Heterocyclic Compounds, Bridged-Ring; Mice; Lactones; Urinary Bladder Neoplasms; Piperidines; Cell Movement; Cell Line, Tumor; Humans; Animals; Wnt Signaling Pathway; beta Catenin; Cell Proliferation

Bladder cancer (BC) is the most common malignant tumor in urinary system. Although chemotherapy one of important adjuvant treatments for BC, drug resistance, non-specific toxicity and severe side effects are major obstacles to BC chemotherapy. Natural products have always been a leading resource antitumor discovery, with advantages excellent effectiveness, low toxicity, multi-targeting potency easy availability. In this study, we evaluated potential anti-tumor effect securinine (SEC), natural alkaloid from Securinega suffruticosa, on cells vitro vivo, delineated underlying mechanism. We found that SEC inhibited proliferation, migration invasion, induced apoptosis vitro, retarded xenograft growth cell vivo. Notably, had promising safety profile because it presented no or normal mice. Mechanistically, inactivated Wnt/β-catenin signaling pathway while activated p38 JNK pathway. Moreover, β-catenin overexpression, inhibitor SB203580 SP600125 both mitigated inhibitory cells. Furthermore, demonstrated synergistic gemcitabine (GEM) Taken together, our findings suggest may exert anti-BC at least through activation pathways, inhibition More meaningfully, indicate GEM-induced killing can be enhanced by combining SEC.