Xing-Xing Fan1, Elaine Lai-Han Leung1, Ying Xie1, Zhong Qiu Liu2, Yan Fang Zheng3, Xiao Jun Yao1, Lin Lin Lu2, Jian Lin Wu1, Jian-Xing He4, Zhong-Wen Yuan1, JunJiang Fu5, Chun-Li Wei1, Jun Huang4, Da Kai Xiao4, Lian Xiang Luo1, Ze Bo Jiang1, Yan-Ling Zhou1, Richard Kin-Ting Kam6, Liang Liu1. 1. 1 State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute For Applied Research in Medicine and Health, Macau University of Science and Technology , Macau (SAR), China . 2. 2 International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine , Guangzhou, China . 3. 3 Fujian University of Traditional Chinese Medicine , College of Pharmacy, Minhoushangjie, Fuzhou, China . 4. 4 State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease , The 1st Affiliated Hospital of Guangzhou Medical College, Guangzhou, China . 5. 5 Key Laboratory of Epigenetics and Oncology, Research Center for Precision Medicine, Southwest Medical University , Luzhou, China . 6. 6 Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong , Hong Kong (SAR), China .
Abstract
AIMS: Systemic diseases often have common characteristics. The aim of this study was to investigate the feasibility of targeting common pathological metabolism to inhibit the progression of malignant and proliferative diseases. RESULTS: Gefitinib-resistant (G-R) nonsmall-cell lung cancer (NSCLC) and rheumatoid arthritis (RA) were studied as conditions representative of malignant and proliferative diseases, respectively. Strong lipogenic activity and high expression of sterol regulatory element-binding protein 1 (SREBP1) were found in both G-R NSCLC cells and synovial fibroblasts from RA patients (RASFs). Berberine (BBR), an effective suppressor of SREBP1 and lipogenesis regulated through reactive oxygen species (ROS)/AMPK pathway, selectively inhibited the growth of G-R NSCLC cells and RASFs but not that of normal cells. It effectively caused mitochondrial dysfunction, activated ROS/AMPK pathway, and finally suppressed cellular lipogenesis and cell proliferation. Addition of ROS blocker, AMPK inhibitor, and palmitic acid significantly reduced the effect of BBR. In an in vivo study, treatment of BBR led to significant inhibition of mouse tumor xenograft growth and remarkably slowed down the development of adjuvant-induced arthritis in rats. Innovation and Conclusion: Targeting ROS/AMPK/lipogenesis signaling pathway selectively inhibited the growth of G-R NSCLC cells and the progress of RASFs in vitro and in vivo, which provides a new avenue for treating malignancies and proliferative diseases. Antioxid. Redox Signal. 28, 339-357.
AIMS: Systemic diseases often have common characteristics. The aim of this study was to investigate the feasibility of targeting common pathological metabolism to inhibit the progression of malignant and proliferative diseases. RESULTS:Gefitinib-resistant (G-R) nonsmall-cell lung cancer (NSCLC) and rheumatoid arthritis (RA) were studied as conditions representative of malignant and proliferative diseases, respectively. Strong lipogenic activity and high expression of sterol regulatory element-binding protein 1 (SREBP1) were found in both G-R NSCLC cells and synovial fibroblasts from RApatients (RASFs). Berberine (BBR), an effective suppressor of SREBP1 and lipogenesis regulated through reactive oxygen species (ROS)/AMPK pathway, selectively inhibited the growth of G-R NSCLC cells and RASFs but not that of normal cells. It effectively caused mitochondrial dysfunction, activated ROS/AMPK pathway, and finally suppressed cellular lipogenesis and cell proliferation. Addition of ROS blocker, AMPK inhibitor, and palmitic acid significantly reduced the effect of BBR. In an in vivo study, treatment of BBR led to significant inhibition of mousetumor xenograft growth and remarkably slowed down the development of adjuvant-induced arthritis in rats. Innovation and Conclusion: Targeting ROS/AMPK/lipogenesis signaling pathway selectively inhibited the growth of G-R NSCLC cells and the progress of RASFs in vitro and in vivo, which provides a new avenue for treating malignancies and proliferative diseases. Antioxid. Redox Signal. 28, 339-357.
Authors: Abdullah M Alnuqaydan; Abdulmajeed G Almutary; Mohd Azam; Bikash Manandhar; Geena Hew Suet Yin; Lee Li Yen; Thiagarajan Madheswaran; Keshav Raj Paudel; Philip M Hansbro; Dinesh Kumar Chellappan; Kamal Dua Journal: Pharmaceutics Date: 2022-05-24 Impact factor: 6.525
Authors: Jeong Hoon Pan; Jingsi Tang; Mersady C Redding; Kaleigh E Beane; Cara L Conner; Yun Jeong Cho; Jiangchao Zhao; Jun Ho Kim; Byungwhi C Kong; Jin Hyup Lee; Jae Kyeom Kim Journal: Genes (Basel) Date: 2019-09-19 Impact factor: 4.096