基于JNK信号通路的S-炔丙基L-半胱氨酸新的分子靶点，天然大蒜衍生物：与胰腺癌体外和体内抗癌活性相关

Title:The JNK Signaling Pathway Is a Novel Molecular Target for S-Propargyl- L-Cysteine, a Naturally-Occurring Garlic Derivatives: Link to Its Anticancer Activity in Pancreatic Cancer In Vitro and In Vivo

Volume: 15 Issue: 7

Author(s): Wei Wang, Jianwen Cheng and Yizhun Zhu

Affiliation:

关键词: 凋亡，化疗，大蒜衍生物，JNK，胰腺癌，S-炔丙基-L-半胱氨酸

摘要: Pancreatic ductal adenocarcinoma (PDA) remains a devastating disease worldwide. Although significant improvement has been made in understanding its pathophysiology, only small portion of patients with PDA are likely to benefit from curative surgery and current chemotherapy. Thus, there is an urgent need for developing novel effective therapeutic approaches to the treatment of PDA. Today, garlic products have become an important source of effective compounds for the treatment of cancer. We have recently identified a novel garlic active component, S-propargyl-L-cysteine (SPRC), an analogue of S-Allyl Cysteine (SAC). Although its anticancer activity has been shown against several cancers, the mechanism of action is not fully understood. The present study was first designed to determine the anticancer activity of SPRC in PDA and the underlying mechanisms of action in vitro and in vivo. Our results demonstrated that SPRC reduced cell viability and colony formation, inhibited cell proliferation, induced G2/M phase cell cycle arrest and apoptosis in human PDA cells with various p53 statuses (HPAC, p53 wt; Panc-1, p53 mt). Furthermore, SPRC inhibited tumor growth in Panc-1 xenograft models. We also demonstrated that SPRC achieved its anticancer effects by regulation of the JNK protein levels through increasing its phosphorylation and decreasing its polyubiquitination-mediated degradation. In conclusion, SPRC has significant anti-PDA activity and the effects do not depend on p53 status, presumably through activating the JNK signaling pathway, providing a basis for the development of this compound as a novel target anticancer therapeutic agent for PDA.

Cite this article as:

Wei Wang, Jianwen Cheng and Yizhun Zhu , The JNK Signaling Pathway Is a Novel Molecular Target for S-Propargyl- L-Cysteine, a Naturally-Occurring Garlic Derivatives: Link to Its Anticancer Activity in Pancreatic Cancer In Vitro and In Vivo, Current Cancer Drug Targets 2015; 15 (7) . https://dx.doi.org/10.2174/1568009615666150602143943