AUTHOR=You Longtai , Dong Xiaoxv , Ni Boran , Fu Jing , Yang Chunjing , Yin Xingbin , Leng Xin , Ni Jian TITLE=Triptolide Induces Apoptosis Through Fas Death and Mitochondrial Pathways in HepaRG Cell Line JOURNAL=Frontiers in Pharmacology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00813 DOI=10.3389/fphar.2018.00813 ISSN=1663-9812 ABSTRACT=

Triptolide isolated from the traditional Chinese herb Tripterygium wilfordii Hook F., possesses anti-tumor, anti-fertility, and anti-inflammatory properties. Triptolide-induced hepatotoxicity has continued to engage the attention of researchers. However, not much is yet known about the cytotoxicity of triptolide, and the precise mechanisms involved. In the present study, we investigated the cytotoxicity of triptolide and its underlying mechanisms, using the in vitro model (HepaRG cell). The results demonstrated that triptolide significantly reduced cell viability and induced apoptosis in HepaRG cells in a dose- and time-dependent manner. Triptolide treatment also provoked reactive oxygen species (ROS) generation and depolarization of mitochondrial membrane potential (MMP). Moreover, triptolide dose-dependently increased the protein expression levels of Fas, Bax, p53, p21, cyclin E, cleaved caspase-3, 8, and 9; and subsequent cleavage of poly (ADP-ribose) polymerase (PARP). However, the protein expression of Bcl-2, cyclin A, and CDK 2 were significantly decreased. These results suggest that triptolide inhibits cell proliferation and induces apoptosis via the Fas death pathway and the mitochondrial pathway.