Abstract
The botanical constituents of Stellera chamaejasme Linn. exhibit various pharmacological and medicinal activities. Neochamaejasmin A (NCA), one main active constituent of S. chamaejasme, inhibits cell proliferation and induces cell apoptosis in several types of tumor cells. However, the antitumor effect of NCA on hepatocellular carcinoma cells is still unclear. In this study, NCA (36.9, 73.7, and 147.5 μM) significantly inhibited hepatoblastoma-derived HepG2 cell proliferation in a concentration-dependent manner. Hoechst 33258 staining and flow cytometry showed that apoptotic morphological changes were observed and the apoptotic rate was significantly increased in NCA-treated HepG2 cells, respectively. Additionally, the levels of Bax, cleaved caspase-3, and cytoplasmic cytochrome c were increased, while the level of Bcl-2 was decreased in NCA-treated HepG2 cells when compared with the control group. Moreover, we found that the reactive oxygen species (ROS) level was significantly higher and the mitochondrial membrane potential was remarkably lower in NCA-treated HepG2 cells than in the control group. Further studies demonstrated that the levels of p-JNK and p-ERK1/2 were significantly upregulated in NCA-treated HepG2 cells, and pretreatment with JNK and ERK1/2 inhibitors, SP600125 and PD0325901, respectively, suppressed NCA-induced cell apoptosis of HepG2 cells. In addition, NCA also significantly inhibited human hepatoma BEL-7402 cell proliferation and induced cell apoptosis through the ROS-mediated mitochondrial apoptotic pathway. These results implied that NCA induced mitochondrial-mediated cell apoptosis via ROS-dependent activation of the ERK1/2/JNK signaling pathway in HepG2 cells.
Highlights
Hepatocellular carcinoma (HCC) is the most commonly occurring solid cancer
We found that Neochamaejasmin A (NCA) significantly inhibited HepG2 cell proliferation in a concentrationdependent manner (Figures 2(a)–2(c))
Chromatin condensation and apoptotic bodies were observed in HepG2 cells (Figure 2(e))
Summary
Hepatocellular carcinoma (HCC) is the most commonly occurring solid cancer. The development of highly malignant tumors and the accompanying poor prognosis are considered to be features of HCC [2, 3]. Surgery is considered to be the staple cure for HCC [4]. During surgery, an amount of liver tissue is removed, resulting in the inability of residual liver tissue to survive after surgery, and surgical treatment can only be a palliative treatment for metastatic liver cancer. It has become the focus of research to try to find a new drug for hepatocellular carcinoma
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