2. Academic Validation
  3. Dual targeting agent Thiotert inhibits the progression of glioblastoma by inducing ER stress-dependent autophagy

Dual targeting agent Thiotert inhibits the progression of glioblastoma by inducing ER stress-dependent autophagy

  • Biomed Pharmacother. 2023 Dec 14:170:115867. doi: 10.1016/j.biopha.2023.115867.
Jianhong Dong 1,  Yiming Qian 2,  Wei Zhang 2,  Qian Wang 2,  Mengxian Jia 3,  Juanqing Yue 4,  Ziwei Fan 3,  Yuanyuan Jiang 2,  Lipei Wang 2,  Yongjie Wang 2,  Zhihui Huang 5,  Lushan Yu 6,  Ying Wang 7
Affiliations

Affiliations

  • 1 Department of Clinical Research Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310053, Zhejiang, China; School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China.
  • 2 School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China.
  • 3 Department of Orthopedics (Spine Surgery), the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
  • 4 Department of Clinical Research Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310053, Zhejiang, China.
  • 5 School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China. Electronic address: huang0069@hznu.edu.cn.
  • 6 Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine of Zhejiang Province, Hangzhou 310024, Zhejiang, China. Electronic address: yuls@zju.edu.cn.
  • 7 Department of Clinical Research Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310053, Zhejiang, China. Electronic address: nancywangying@163.com.
PMID: 38101281 DOI: 10.1016/j.biopha.2023.115867
Abstract

Glioblastoma (GBM) is the most aggressive and lethal type of tumor in the central nervous system, characterized by a high incidence and poor prognosis. Thiotert, as a novel dual targeting agent, has potential inhibitory effects on various tumors. Here, we found that Thiotert effectively inhibited the proliferation of GBM cells by inducing G2/M cell cycle arrest and suppressed the migratory ability in vitro. Furthermore, Thiotert disrupted the thioredoxin (Trx) system while causing cellular DNA damage, which in turn caused endoplasmic reticulum (ER) stress-dependent Autophagy. Knockdown of ER stress-related protein ATF4 in U251 cells inhibited ER stress-dependent Autophagy caused by Thiotert to some extent. Orthotopic transplantation experiments further showed that Thiotert had the same anti-GBM activity and mechanism as in vitro. Conclusively, these results suggest that Thiotert induces ER stress-dependent Autophagy in GBM cells by disrupting redox homeostasis and causing DNA damage, which provides new insight for the treatment of GBM.

Keywords

Autophagy; DNA damage; ER stress; GBM; Thiotert; Trx system.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z