Neochamaejasmin A Induces Mitochondrial-Mediated Apoptosis in Human Hepatoma Cells via ROS-Dependent Activation of the ERK1/2/JNK Signaling Pathway

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.

Phytochemical composition and bioactive effects of ethyl acetate fraction extract (EAFE) of Glechoma hederacea L.

“…is neochamaejasmin A, which also triggered MMP disorder, up‐regulated the levels of Bax, cleaved caspase‐3 and down‐regulated the level of Bcl‐2 in HepG2 cells. Therefore, these results indicated that neochamaejasmin A could induce HepG2 and BEL‐7402 cell apoptosis through the mitochondrial apoptotic pathway (Ding et al., 2020).…”

Neochamaejasmin A Induces Apoptosis in Human Osteosarcoma MG-63 Cells via Mitochondrial Dysfunction and Phosphatidylinositol 3 Kinase/Protein Kinase B/Glycogen Synthase Kinase-3-Beta Signaling Pathway

“…NCA is a new biologically active compound isolated from Stellera chamaejasme. NCA has been reported to possess antitumor effects on several types of human cancers [11,12] . However, few studies focused on its effect on osteosarcoma.…”

“…Exposure with NCA could block cell cycle progression at the Growth 1 (G1) phase by activating cyclindependent kinase inhibitor p21 and induce apoptosis through Fas Cell Surface Death Receptor (FAS)/ caspase dependent pathway [11] . Recently, Ding et al reported that NCA could inhibit the proliferation of human hepatoma HepG2 cells and induce mitochondrialmediated apoptosis via Extracellular Signal-Regulated Kinase 1/2 (ERK1/2)/c-Jun N-terminal Kinase (JNK) signaling pathway [12] . However, the antitumor effect of NCA on human osteosarcoma cells has not yet been investigated.…”

Shenxiong glucose injection inhibits oxidative stress and apoptosis to ameliorate isoproterenol-induced myocardial ischemia in rats and improve the function of HUVECs exposed to CoCl2

“…There is accumulating evidence that excessive ROS induces apoptosis by phosphorylating and activating the ERK1/2 pathway ( Ding Y. et al, 2020 ). Apoptosis regulation of HUVECs involves phosphorylation of the ERK signaling pathway ( Mi et al, 2019 ).…”