Molecular mechanism and inhibitory targets of dioscin in HepG2 cells. (October 2018)

• Record Type: Journal Article
• Authors: Zhang, Ying-Shuo; Ma, Yi-Long; Thakur, Kiran; Hussain, Sayed Sajid; Wang, Jun; Zhang, Qi; Zhang, Jian-Guo; Wei, Zhao-Jun
• Is Part Of: Food and chemical toxicology. Volume 120(2018)
• Page Start: 143
• Page End: 154
• Publication Date: 2018-10
• Subjects: Polygonatum sibiricum -- Dioscin -- Cell cycle -- Apoptosis -- Molecular mechanism; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.07.016
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Dioscin has been known for its anti-cancer activity; however, its detailed molecular mechanisms have not been studied so far. Herein, we evaluated the anti-cancer activity of dioscin for proliferation inhibition and apoptosis in HepG2 cancer cells. Initially, dioscin was purified and identified from Polygonatum sibiricum by HPLC, MS, and NMR analysis, respectively. Dioscin inhibited the cell multiplication at IC50 of 8.34 μM, altered the cell morphology, arrested the cell cycle in G2/M phase and led to considerable programmed cell death. Furthermore, it has efficiently promoted the mitochondrial pathway and death receptor pathway. The inhibition of Caspase-8 and Caspase-9 proteins in these pathways abolished the dioscin induced apoptosis significantly; while dioscin inhibited the PI3K/Akt/mTOR pathway. Moreover, dioscin exposure led to enhanced intracellular ROS generation and the mRNA expression of JNK gene which emphasized their involvement in the apoptosis process in HepG2 cells. Graphical abstract: Highlights: Dioscin arrested cell cycle in G2/M, affected cell cycle genes and proteins expression. Dioscin could regulate apoptosis of HepG2 cells via death receptor and mitochondrial pathway. Dioscin treatment resulted in the generation of intracellular ROS of HepG2 cells.