Apoptotic effect of chromanone derivative, hyrtiosone A from marine demosponge Hyrtios erectus in hepatocellular carcinoma HepG2 cells.

ABSTRACT

The tumor suppressor proteins p53 and p27 exhibited a significant role in the survival of cells and regulation of cellular division and growth. In majority of the human tumors, particularly in hepatocellular carcinoma, these proteins are inactivated by mutation or deletion, and are considered to predict the pathophysiology related to liver cancer. The present study evaluated the activation of the p53 and p27 pathways as a useful therapeutic tool to attenuate hepatocellular carcinoma. Three undescribed homologous chromanone derivatives, hyrtiosones A-C were isolated from the organic extract of marine demosponge Hyrtios erectus (family Thorectidae). Preliminary bioactivity assessments found that hyrtiosone A exhibited prospective anti-inflammatory (IC50 1.02-1.86 mM) and antioxidant (IC50 0.74-0.83 mM) properties. Molecular docking analysis of the hyrtiosones using p53-murine double minute complex revealed lesser docking parameters for hyrtiosone A (binding energy -11.12 kcal mol-1, docking score -12.18 kcal mol-1) thereby attributing its greater bioactivity. Hyrtiosone A was furthermore analyzed for in vitro anticancer activity in hepatocellular carcinoma HepG2 cells. Morphological assessment of hyrtiosone A treated HepG2 cell line by acridine orange/ethidium bromide fluorescence staining revealed greater number of apoptotic cells, and was found to be comparable with the cells treated with the standard doxorubicin. Further the Annexin V-fluorescein isothiocyanate assay of hyrtiosone A treated HepG2 cell line by flow cytometry displayed greater number of early apoptotic cells (51.24%) than that exhibited by the standard (21.45%). Cell cycle distribution analysis showed that hyrtiosone A arrested the S and G2/M phase of cell cycle and upregulate the gene expression of p53 and p27 in hepatocellular carcinoma HepG2 cells.