Induction of apoptosis by casticin in cervical cancer cells: reactive oxygen species-dependent sustained activation of Jun N-terminal kinase

Abstract

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 cJun 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.

Vitexicarpin Induces Apoptosis in Human Prostate Carcinoma PC-3 Cells through G2/M Phase Arrest

“…Because excessive ROS production can induce depolarization of MMP, next we performed flow cytometric analysis to determine MMP in control and vitexicarpin-treated cells. The data showed that MMP in vitexicarpin-treated PC-3 cells was significantly decreased which is in line well with previous result found in Hela cells (Chen et al, 2011;Zeng et al, 2012).…”

“…It showed that vitexicarpin dosedependently induced apoptosis in PC-3 cells. Previous studies have indicated that vitexicarpin induced apoptosis in hepatocellular carcinoma HepG2 (Yang et al, 2011;He et al, 2012) and human cervical cancer cells (Chen et al, 2011;Zeng et al, 2012). Also, we found vitexicarpin induced apoptotic cell death in PC-3 cells in a dosedependent manner.…”

“…Natural products have traditionally provided a rich source of drugs for many diseases, including cancer. Previous studies have indicated that vitexicarpin has inhibitory activities against various cancer cell lines (Shen et al, 2009;Chen et al, 2011;Koh et al, 2011;Yang et al, 2011;He et al, 2012;Zeng et al, 2012), while its effects on human prostate cancer cells remain uninvestigated. In the present paper, we showed that vitexicarpin is able to inhibit growth of human PC-3 prostate cancers.…”

“…A number of recent pharmacological reports indicated that vitexicarpin induces growth inhibition, cell cycle arrest, and apoptosis in various cancer cells including the human cervical cancer cell line Hela (Chen et al, 2011;Zeng et al, 2012), hepatocellular carcinoma cell line HepG2 (Yang et al, 2011;He et al, 2012), lung epithelial cell line A549 (Koh et al, 2011), and leukemic cell line K562 (Shen et al, 2009). Molecular mechanism studies showed that vitexicarpin induces apoptosis via activation of c-Jun N-terminal kinase (JNK) in Hela cells (Zeng et al, 2012), inactivation NF-κB in A549 cells (Koh et al, 2011), Caspase-3 activation in K562 cells (Shen et al, 2009), etc. So far, there is no information available on its effect on human prostate carcinoma cells.…”

Vitexicarpin inhibits overexpression of GNAO1 and plays a role in gastric cancer cell proliferation and apoptosis

“…Vitexicarpinis reported to induce growth inhibition, cell cycle arrest, and apoptosis in human cervical cancer cell line HeLa (Chen et al, 2011;Zeng et al, 2012), hepato-…”