Lithium chloride induces apoptosis by activating endoplasmic reticulum stress in pancreatic cancer.

Oct 09, 2023

Experts: Hao Wu,Yin Zhang,Jiawei Liang,Jianzhuang Wu,Yixuan Zhang,Haochen Su,Qiyue Zhang,Yonghua Shen,Shanshan Shen,Lei Wang,Xiaoping Zou,Cheng Hang,Shu Zhang,Ying Lv

Lithium compounds, a classic class of metal complex medicine that target GSK 3β and are widely known as mood-stabilizer, have recently been reported as potential anti-tumor drugs. The objective of this investigation was to explore the anticancer potential of lithium chloride (LiCl) and elucidate its mode of action in pancreatic cancer cells. The MTT, colony formation, and Edu assay were used to evaluate the impact of LiCl on pancreatic cancer cell proliferation. Various methods were employed to investigate the anti-tumor activity of LiCl and its underlying mechanisms. Cell cycle analysis and apoptosis detection assays were utilized for in vitro experiments, while the orthotopic pancreatic cancer mouse model was employed to evaluate the effectiveness of LiCl treatment in vivo. Furthermore, the impact of LiCl on the proliferation of patient-derived organoids was also studied. The results demonstrated that LiCl inhibited the proliferation of pancreatic cancer (PC) cells, induced G2/M phase arrest, and activated apoptosis. Notably, the triggering of endoplasmic reticulum (ER) stress by LiCl was observed, leading to the activation of the PERK/CHOP/GADD34 pathway, which subsequently promoted apoptosis in PC cells. In the future, Lithium compounds could become an essential adjunct in the treatment of human pancreatic cancer.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

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ABOUT THE EXPERTS

Hao Wu,Yin Zhang,Jiawei Liang,Jianzhuang Wu,Yixuan Zhang,Haochen Su,Qiyue Zhang,Yonghua Shen,Shanshan Shen,Lei Wang,Xiaoping Zou,Cheng Hang,Shu Zhang,Ying Lv

Hao Wu

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 Jiangsu, PR China; Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China; Department of Geriatrics, Nanjing Red Cross Hospital, No. 242, Baixia Road, Qinhuai District, Nanjing 21000 Jiangsu, PR China.

Yin Zhang

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 Jiangsu, PR China; Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China.

Jiawei Liang

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 Jiangsu, PR China; Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China.

Jianzhuang Wu

Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210033 Jiangsu, PR China.

Yixuan Zhang

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 Jiangsu, PR China; Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China.

Haochen Su

Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China; Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008 Jiangsu, PR China.

Qiyue Zhang

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 Jiangsu, PR China; Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China.

Yonghua Shen

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 Jiangsu, PR China; Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China.

Shanshan Shen

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 Jiangsu, PR China; Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China.

Lei Wang

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 Jiangsu, PR China; Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China.

Xiaoping Zou

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 Jiangsu, PR China; Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China; Department of Gastroenterology, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210023 Jiangsu, PR China.

Cheng Hang

Department of Gastroenterology, Taicang Affiliated Hospital of Soochow University, The First People’s Hospital of Taicang, Taicang 215400 Jiangsu, PR China. Electronic address: hc5626@suda.edu.cn.

Shu Zhang

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 Jiangsu, PR China; Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China. Electronic address: zhangsgastro@nju.edu.cn.

Ying Lv

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 Jiangsu, PR China; Institute of Pancreatology, Nanjing University, Nanjing 210008 Jiangsu, PR China; Department of Gastroenterology, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210023 Jiangsu, PR China. Electronic address: lvying@njglyy.com.