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Pharmaceuticals 2016, 9(2), 18; doi:10.3390/ph9020018

A Selenium Containing Inhibitor for the Treatment of Hepatocellular Cancer

1
Department of Surgery, Pennsylvania State University, Hershey, PA 17033, USA
2
Department of Pharmacology, Pennsylvania State University, Hershey, PA 17033, USA
3
Medical University of South Carolina, Charleston, SC 29425, USA
4
Bon Secours Pediatric Associates, 5875 Bremo Road, Richmond, VA 23226, USA
5
Department of Public Health Sciences, Pennsylvania State University, Hershey, PA 17033, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Ashkan Emadi and Jean Jacques Vanden Eynde
Received: 4 January 2016 / Revised: 11 March 2016 / Accepted: 16 March 2016 / Published: 24 March 2016
(This article belongs to the Special Issue Chemotherapeutic Agents)
View Full-Text   |   Download PDF [2466 KB, uploaded 24 March 2016]   |  

Abstract

Hepatocellular carcinoma (HCC) is the third most deadly cancer in the world. New treatment strategies are desperately needed due to limited standard therapies. Activation of the Erk, Akt, and STAT3pathways is implicated in the prognosis of HCC. The Se,Se′-1,4-phenylenebis(1,2-ethanediyl) bisisoselenourea (PBISe), is a selenium-containing MAPK and PI3 kinase inhibitor, effectively inhibit tumorigenesis in a variety of experimental models. The aim of our study is to demonstrate the potential role of PBISe in the treatment of HCC. The anti-proliferative and pro-apoptotic ability of PBISe is studied in vitro in four human HCC cell lines and in vivo in a spontaneous murine HCC model. Inhibition of cancer growth was performed by cell viability assay and apoptosis by caspase 3/7, PARP cleavage, annexin-V, and TUNEL assays. Role of PBISe on PI3 kinase, MAPK and STAT3 signaling is determined by Western blotting. In vivo effects of PBISe on tumor sizes were monitored using MRI in a spontaneous murine HCC. Liver tissues from the PBISe-treated mice are analyzed for angiogenesis, proliferation, and signaling pathway markers. Overall, PBISe activated caspase-3/7 and increased DNA fragmentation, which is positively correlated with the increased PARP cleavage. PBISe promoted apoptosis by inhibiting PI3K, MAPK, and STAT3 signaling with significant reduction in the tumor sizes (p < 0.007). PBISe-treated tumors reduced survival marker PCNA, and angiogenesis markers Vegf-A, Vegf-R3 and CD34. These results demonstrate the chemotherapeutic effects of PBISe, by inhibiting tumor growth and facilitating tumor apoptosis for HCC treatment. View Full-Text
Keywords: inhibition; hepatocellular cancer; selenium; apoptotic and angiogenesis markers inhibition; hepatocellular cancer; selenium; apoptotic and angiogenesis markers
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Tagaram, H.R.S.; Desai, D.; Li, G.; Liu, D.; Rountree, C.B.; Gowda, K.; Berg, A.; Amin, S.; Staveley-O’Carroll, K.F.; Kimchi, E.T. A Selenium Containing Inhibitor for the Treatment of Hepatocellular Cancer. Pharmaceuticals 2016, 9, 18.

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