Abstract 2133: Phenylenebis(1,2-ethanediyl)bisisoselenourea (PBISe), a novel selenium drug for the treatment of hepatocellular cancer (HCC)

Abstract

Abstract Hepatocellular cancer (HCC) is an aggressive tumor that frequently arises in a setting of chronic liver disease and cirrhosis. Appearing 20 to 30 years from initial insult, it is more likely to be discovered in its late stage. The median survival following diagnosis is approximately 6 to 20 months. Although the definitive treatment is tumor resection, most patients are not eligible because of tumor extent or underlying liver dysfunction. Alternative chemopreventive approach in reducing HCC mortality is to be explored. Earlier we have shown the efficacy of PBISe against colon adenocarcinoma and metastatic melanoma with a negligible systemic toxicity in animal studies. In the present study, we intend to demonstrate the chemotherapeutic effects of PBISe on the human HCC. We analyzed the role of PBISe and the underlying mechanism in HCC. PBISe in our study suppressed cell growth, and induce apoptosis. Evaluation of PBISe was performed in vitro on human SK-HEP-1, HepG2, C3A and HUH-7 cells by cellular viability, caspase 3/7 activity, annexin-V expression, DNA fragmentation by Tunnel, cell cycle analysis and AKT, ERK, STAT, SAPK/JNK phosphorylation. PBISe promotes apoptosis by upregulating caspase 3/7, annexin-V, and cPARP. Increased DNA fragmentation was observed with PBISe in all the HCC cell lines tested. PBISe also mediated the cellular proliferation by AKT signaling and downstream pPRAS40 by inducing the cell cycle arrest at G2-M phase. Decreased pERK, pSTAT and pAKT shows that PBISe has a potential to target several signaling pathways. Overall our results suggest that PBISe is a potent chemotherapeutic agent with novel properties for the treatment of HCC. The chemotherapeutic effect of PBISe in the murine HCC model will be discussed. Supported by Penn State Deans Feasibility Grant to H.R.T, NIH RO3 CA 137763-01 to D. D., NIH KO8 417-67HY to K.S.O.C. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2133. doi:10.1158/1538-7445.AM2011-2133