Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells

BMC Cancer

Research Article

Karvannan Kanchana¹  Peng Zou¹  Guang Liang¹  Peng Zhong¹  Huiping Zhou¹  Wenbo Chen¹  Qiaoyou Weng²  Minxiao Chen³  Jiansong Ji⁴  Langchong He⁵  Xiuhua Zhang⁶ 

[1] Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, 325035, Wenzhou, Zhejiang, China;Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, 325035, Wenzhou, Zhejiang, China;Department of Interventional Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, 323000, Lishui, Zhejiang, China;Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, 325035, Wenzhou, Zhejiang, China;Department of Pharmacy, the First Affiliated Hospital of Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China;Department of Interventional Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, 323000, Lishui, Zhejiang, China;School of Pharmacy, Health Science Center, Xi’an Jiaotong University, 710061, Xi’an, Shanxi, China;School of Pharmacy, Health Science Center, Xi’an Jiaotong University, 710061, Xi’an, Shanxi, China;Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, 325035, Wenzhou, Zhejiang, China;Department of Pharmacy, the First Affiliated Hospital of Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China;

关键词: Cell cycle arrest;    CHOP;    Curcumin analog;    ER stress;    Prostate cancer;    PC-3;    ROS;   

DOI  :  10.1186/s12885-015-1851-3

 received in 2015-05-18, accepted in 2015-10-26,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundProstate cancer is the most commonly diagnosed malignancy among men. The Discovery of new agents for the treatment of prostate cancer is urgently needed. Compound WZ35, a novel analog of the natural product curcumin, exhibited good anti-prostate cancer activity, with an IC50 of 2.2 μM in PC-3 cells. However, the underlying mechanism of WZ35 against prostate cancer cells is still unclear.MethodsHuman prostate cancer PC-3 cells and DU145 cells were treated with WZ35 for further proliferation, apoptosis, cell cycle, and mechanism analyses. NAC and CHOP siRNA were used to validate the role of ROS and ER stress, respectively, in the anti-cancer actions of WZ35.ResultsOur results show that WZ35 exhibited much higher cell growth inhibition than curcumin by inducing ER stress-dependent cell apoptosis in human prostate cells. The reduction of CHOP expression by siRNA partially abrogated WZ35-induced cell apoptosis. WZ35 also dose-dependently induced cell cycle arrest in the G2/M phase. Furthermore, we found that WZ35 treatment for 30 min significantly induced reactive oxygen species (ROS) production in PC-3 cells. Co-treatment with the ROS scavenger NAC completely abrogated the induction of WZ35 on cell apoptosis, ER stress activation, and cell cycle arrest, indicating an upstream role of ROS generation in mediating the anti-cancer effect of WZ35.ConclusionsTaken together, this work presents the novel anticancer candidate WZ35 for the treatment of prostate cancer, and importantly, reveals that increased ROS generation might be an effective strategy in human prostate cancer treatment.

【 授权许可】

CC BY   
© Zhang et al. 2015