DIFFERENTIAL REGULATION OF P53, C-MYC, BCL-2 AND BAX PROTEIN EXPRESSION DURING APOPTOSIS INDUCED BY WIDELY DIVERGENT STIMULI IN HUMAN HEPATOBLASTOMA CELLS

Apoptosis of HepG2 cells triggered by various agents is characterized in an attempt to delineate the common apoptosis signaling pathway in h uman hepatoma cells. Several hallmarks of apoptosis, including DNA lad dering, chromatin condensation and fragmentation, and an apoptosis spe cific cleavage of 28S and 18S ribosomal RNA were observed after treatm ent with curcumin. Curcumin treatment however did not alter the expres sion levels of Bcl-2 and Bax proteins, p53 protein accumulated slowly and decreased abruptly after reaching the maximum. Conversely, c-Myc p rotein decreased initially and subsequently increased preceding the on set of apoptosis. The accumulation of p53 protein is not due to increa sed levels of p53 mRNA and does not result in growth arrest. Staurospo rine, quinacrine, ultraviolet irradiation, hydrogen peroxide, and cycl ohexamide are all capable of triggering apoptosis in HepG2 cells. Whil e most of these agents affect the expression levels of p53 and c-Myc s imilarly, none of them altered the expression levels of the Bcl-2 and Bax proteins. In conclusion, these data suggest that p53 and c-Myc may play a more important role in the apoptosis signaling pathway in HepG 2 cells, than the bcl-2 gene family.