Bauerenol, a triterpenoid from Indian Suregada angustifolia: Induces reactive oxygen species–mediated P38MAPK activation and apoptosis in human hepatocellular carcinoma (HepG2) cells

Abstract

The triterpenoid, bauerenol, from Suregada angustifolia (Baill. ex Muell.-Arg.) Airy Shaw (Euphorbiaceae) was screened for anti-cancer property using hepatocellular carcinoma cell line, HepG2. Bauerenol exhibited growth inhibitory and apoptosis inducing potential against HepG2 cancer cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxic assay revealed that bauerenol treatment significantly reduced the growth of HepG2 cells in a time- and dose-dependent manner with 50% growth inhibitory concentration doses of 45 and 25 µg/mL at 24 and 48 h treatments, respectively. Bauerenol-induced cell death reflected apoptotic morphological features, that is, cell membrane blebbing, vacuolization, chromatin condensation, and nuclear fragmentation. In addition, bauerenol treatment diminished the mitochondrial membrane potential, by inducing the efflux of cytochrome c, downregulating the levels of anti-apoptotic Bcl-2 as well as upregulating the levels of pro-apoptotic Bax, and inducing caspase activation and poly (ADP-ribose) polymerase cleavage. Moreover, bauerenol treatment activates p38MAPK and inactivates the anti-apoptotic kinases Akt and ERK1/2 through the induction of reactive oxygen species. Furthermore, bauerenol-mediated S-phase arrest was associated with downregulation of cell cycle-rate-limiting factor (cyclin D1) and upregulation of cyclin-dependent kinase inhibitor p21 and tumor suppressor p53. Interestingly, pre-treatment of cells with reactive oxygen species inhibitor and p38 inhibitor significantly decreases bauerenol-induced cytotoxicity, Bax upregulation, and p38 activation. This study clearly states that bauerenol induces cell cycle arrest and apoptosis through the reactive oxygen species-dependent p38MAPK activation in HepG2 cancer cells.

Assessment of anticancer activity of Pulicaria undulata on hepatocellular carcinoma HepG2 cell line

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<p>High Inflammatory Factor Grading Predicts Poor Disease-Free Survival in AJCC Stage I-II Hepatocellular Carcinoma Patients After R0 Resection</p>

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Identification of H2O2 induced oxidative stress associated microRNAs in HLE-B3 cells and their clinical relevance to the progression of age-related nuclear cataract

“…Since it was co-regulated by three miRNAs, the specific mechanism needs further research. Mitogen-activated protein kinase 14 (MAPK14) is a member of the MAP kinase family, which is activated by various environmental stresses and proinflammatory cytokines [ 43 , 44 ]. Although there is no report considering the connection between MAPK14 and cataract, our finding suggests the possibility of MAPK14’s involvement in cataract formation via its response to oxidative stress.…”