As2O3 induces apoptosis in human hepatocellular carcinoma HepG2 cells through a ROS-mediated mitochondrial pathway and activation of caspases.
Arsenic trioxide (As2O3) has been shown to induce apoptosis in hepatocellular carcinoma cells. However, the molecular mechanism of As2O3-induced apoptosis in the hepatocellular carcinoma cells remains poorly understood. Here, we investigated the impact of As2O3 exposure on the human hepatocellular carcinoma cell line HepG2 and examined the underlying mechanism of cell death. As2O3 induced apoptosis of HepG2 cells in a dose- and time-dependent manner and caused a massive production of reactive oxygen species (ROS). The antioxidant N-acetylcysteine (NAC) was able to prevent As2O3-induced cell death, implying an involvement of ROS in the induction of As2O3-triggered apoptosis. Furthermore, As2O3 initiated apoptosis by triggering of the mitochondria apoptotic pathway as indicated by inhibited Bcl-2 expression, a collapse of the mitochondrial membrane potential (MMP), release of cytochrome c and activation of the caspase cascade. However, these As2O3-induced events can be prevented by NAC. Taken together, these findings suggest that the As2O3 induced apoptosis through a ROS-mediated mitochondrial pathway and activation of caspases.
Department of Traditional Chinese Medicine, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi 710038, PR China.
Lin
L
Jiang
Department of Traditional Chinese Medicine, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi 710038, PR China.
Le
L
Wang
Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi 710038, PR China.
Lei
L
Chen
Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University Xi'an 710032, PR China.
Guo-Hong
GH
Cai
Department of Traditional Chinese Medicine, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi 710038, PR China.
Qin-You
QY
Ren
Research Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi 710032, PR China.
Jian-Zong
JZ
Chen
Department of Traditional Chinese Medicine, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi 710038, PR China.
Heng-Jun
HJ
Shi
Department of Respiratory, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi 710038, PR China.
Yong-Hong
YH
Xie
Arsenic trioxide; caspase; hepatocellular carcinoma; mitochondrial pathway; reactive oxygen species