Curcumin derivative WZ35 efficiently suppresses colon cancer progression through inducing ROS production and ER stress-dependent apoptosis.
Colon cancer is characterized by its fast progression and poor prognosis, and novel agents of treating colon cancer are urgently needed. WZ35, a synthetic curcumin derivative, has been reported to exhibit promising antitumor activity. Here, we investigated the in vitro and in vivo activities of WZ35 and explored the underlying mechanisms in colon cancer cell lines. WZ35 treatment significantly decreased the cell viability associated with G2/M cell cycle arrest and apoptosis induction in colon cancer cell lines. We also show that WZ35 is highly effective in inhibiting tumor growth in a CT26 xenograft mouse model. Mechanistically, WZ35 treatment significantly induced reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress in CT26 cells. Abrogation of ROS production by N-acetylcysteine (NAC) co-treatment almost totally reversed the WZ35-induced cell apoptosis and ER stress activation. Inhibition of p-PERK by GSK2606414 can significantly reverse WZ35-induced cell apoptosis in CT26 cells. Taken together, the curcumin derivative WZ35 exhibited anti-tumor effects in colon cancer cells both in vitro and in vivo, via a ROS-ER stress-mediated mechanism. These findings indicate that activating ROS generation could be an important strategy for the treatment of colon cancers.
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical UniversityWenzhou, Zhejiang 325035, China; Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Science, Wenzhou Medical UniversityWenzhou, Zhejiang 325035, China; School of Pharmaceutical Science, Binzhou Medical UniversityYantai, Shandong 264003, China.
Junru
J
Zhang
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
Zhiguo
Z
Feng
School of Pharmaceutical Science, Binzhou Medical University Yantai, Shandong 264003, China.
Chunhua
C
Wang
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
Huiping
H
Zhou
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
Weidong
W
Liu
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
Karvannan
K
Kanchana
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
Xuanxuan
X
Dai
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
Peng
P
Zou
Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Science, Wenzhou Medical UniversityWenzhou, Zhejiang 325035, China; Kosair Children's Hospital Research Institute, Department of Pediatrics of The University of LouisvilleLouisville, KY 40202, USA.
Junlian
J
Gu
Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Science, Wenzhou Medical UniversityWenzhou, Zhejiang 325035, China; Kosair Children's Hospital Research Institute, Department of Pediatrics of The University of LouisvilleLouisville, KY 40202, USA.
Lu
L
Cai
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
Guang
G
Liang
Colon cancer; apoptosis; curcumin derivative; endoplasmic reticulum stress; reactive oxygen species