INVESTIGATION OF THE CELLULAR EFFECTS OF HSP90 INHIBITION ON HEPATOCELLULAR CARCINOMA CELLS

Abstract

Heat shock protein 90 (Hsp90) has been identified as a potential therapeutic target for hepatocellular carcinoma as it was found to facilitate the folding of oncoproteins. There are two naturally occuring Hsp90 inhibitors, geldanamycin and radicicol. Previous studies had demonstrated that derivatives of geldanamycin such as 17-AAG, were able to reduce cell growth and induce apoptosis in HCC cells. However, geldanamycin and its derivatives possess a quinone moiety that is likely to induce cellular cytotoxicity. As a result, it remains questionable whether the observed effects in the HCC cells were attributed to the inhibition of Hsp90?s functionality or the quinone moiety. Hence, this project was undertaken to investigate the effects of Hsp90 inhibition, using radicicol and study the molecules that were deregulated in HCC cells after treatment with 17-AAG. This study had demonstrated the cellular effects of Hsp90 inhibition in HCC cells. It also uncovered the downstream molecular effects of Hsp90 inhibition in HCC cells and consequently, its impact on various biochemical pathways. These findings may be valuable in the exploitation of Hsp90 as a therapeutic application for treating HCC.