Casticin, a polymethoxyflavone from Fructus viticis used as an
anti-inflammatory agent in
Chinese traditional medicine, has been reported to have anti-
cancer activity. The purpose of this study was to examine the apoptotic activity of
casticin on human
cervical cancer cells and its molecular mechanism. We revealed a novel mechanism by which
casticin-induced apoptosis occurs and showed for the first time that the apoptosis induced by
casticin is mediated through generation of
reactive oxygen species (ROS) and sustained activation of
c-Jun N-terminal kinase (JNK) in HeLa cells.
Casticin markedly increased the levels of intracellular ROS and induced the expression of phosphorylated JNK and c-Jun
protein. Pre-treatment with
N-acetylcysteine and
SP600125 effectively attenuated induction of apoptosis by
casticin in HeLa cells. Moreover,
casticin induced ROS production and apoptotic cell death in other
cervical cancer cell lines, such as CasKi and SiHa. Importantly,
casticin did not cause generation of ROS or induction of apoptosis in normal human peripheral blood mononuclear cells and embryonic kidney epithelium 293 cells. These results suggest that ROS generation and sustained JNK activation by
casticin play a role in
casticin-induced apoptosis and raise the possibility that treatment with
casticin might be promising as a new
therapy against human
cervical cancer.