Dual role of reactive oxygen species in autophagy and apoptosis induced by compound PN in prostate cancer cells

Molecular & Cellular Toxicology

article

Choi, Hyeun Deok¹  Ahn, Soon-Cheol²  Kim, Kwang-Youn³  Park, Kwang Il⁴  Kim, Sang-Hun⁵  Park, Sul-Gi²  Yu, Sun-Nyoung²  Kim, Young-Woo⁶  Kim, Dong Seob⁷  Chung, Kyung Tae⁸ 

[1] Healthcare Research Institute;Department of Microbiology and Immunology, Pusan National University School of Medicine;Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM);Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University;Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine;School of Korean Medicine, Dongguk University;Department of Biomaterial Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University;Department of Clinical Laboratory Science, Dong-Eui University

关键词: Apoptosis;    Autophagy;    Human prostate cancer;    Pharbitis nil (L.) choisy;    Reactive oxygen species;   

DOI  :  10.1007/s13273-020-00107-4

来源: Korean Society of Toxicogenomics and Toxicoproteomics

【 摘 要 】

Background Pharbitis nil (L.) Choisy (PN) is used as a traditional herb in East Asia and exhibits anti-parasitic, purgative, diuretic, anti-inflammatory, and anti-cancer activities. However, the molecular mechanisms underlying the anti-cancer activity are not well understood. Objective This study aims to elucidate the effects of reactive oxygen species (ROS), generated after treatment with the compound PN, on the induction of apoptosis and autophagy, which are pathways that underly the mechanisms of cell death and cell survival in human prostate cancer cells. Results The MTT assay and western blot analysis were used to assess the effects of compound PN on cell viability and the expression of apoptosis- and autophagy-related proteins in prostate cancer PC-3 cells. The effects of PN on apoptosis (via annexin V/propidium iodide staining), autophagy (via acridine orange staining), and ROS (via DCFH-DA staining) were investigated using flow cytometry. Compound PN induced the production of intracellular and mitochondrial ROS leading to increased apoptosis and autophagy in PC-3 cells. Interestingly, pretreatment with N-acetyl-l-cysteine (NAC), an intracellular ROS scavenger, enhanced compound PN-induced apoptosis, but reduced levels of autophagy. In contrast, pretreatment with diphenyleneiodonium (DPI), an inhibitor of mitochondrial ROS, reduced compound PN-induced apoptosis and enhanced autophagy. Inhibition of autophagy led to acceleration of apoptosis in a PN-induced ROS-dependent manner. Compound PN-induced ROS production from two different sources, an intracellular source and mitochondrial source. ROS production in these differing locations had different effects on apoptosis and autophagy. They acted either by promoting cell death or cell survival through regulating autophagy to either escape or enhance apoptotic cell death. Conclusion This crosstalk between ROS-activated signals in apoptosis and autophagy induction by PN provides new insights into the molecular mechanisms of this compound and suggests that PN may be a potential therapy for prostate cancer treatment.

【 授权许可】

Unknown