title: Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells.
abstract: BACKGROUND
  Prostate 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.
  
  
  METHODS
  Human 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.
  
  
  RESULTS
  Our 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.
  
  
  CONCLUSIONS
  Taken 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.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shanxi, China. wzzhangxiuhua@126.com.|Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, 325035, Zhejiang, China. wzzhangxiuhua@126.com.|Department of Pharmacy, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. wzzhangxiuhua@126.com.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, 325035, Zhejiang, China. 15258693935@163.com.|Department of Pharmacy, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. 15258693935@163.com.
authors.forename: Minxiao
authors.initials: M
authors.lastname: Chen
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, 325035, Zhejiang, China. 250182876@qq.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, 325035, Zhejiang, China. kanchan.bio86@gmail.com.
authors.forename: Karvannan
authors.initials: K
authors.lastname: Kanchana
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, 325035, Zhejiang, China. 236285127@qq.com.|Department of Interventional Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, Zhejiang, China. 236285127@qq.com.
authors.forename: Qiaoyou
authors.initials: Q
authors.lastname: Weng
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, 325035, Zhejiang, China. 18312912151@163.com.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Chen
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, 325035, Zhejiang, China. 794475962@qq.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhong
authors.affiliation: Department of Interventional Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, Zhejiang, China. jjstcty@sina.com.
authors.forename: Jiansong
authors.initials: J
authors.lastname: Ji
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, 325035, Zhejiang, China. vcuzhouhuiping@163.com.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shanxi, China. helc@mail.xjtu.edu.cn.
authors.forename: Langchong
authors.initials: L
authors.lastname: He
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, 325035, Zhejiang, China. wzmcliangguang@163.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015870:Gene Expression; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; D003474:Curcumin