Hany A. Omar, Jui-Hsiang Hung and Taleb H. Al-Tel
Department of Pharmacology, College of Pharmacy, University of Sharjah, Sharjah, UAE; Sharjah Institute for Medical and Health Sciences Research, University of Sharjah, Sharjah, UAE
Background: OSU-2S is a novel anti-cancer agent that was designed and developed to selectively avert the immunosuppressive effects and related toxicities of its predecessor analog, fingolimod (FTY720). In the current study, we aimed to test the potential synergy between OSU-2S and sorafenib the first line chemotherapeutic agent for hepatocellular carcinoma as a new therapeutic option. Such combination can exploit the maximal benefit through synergistic targeting of the cancer cell survival signaling pathways.
Methods: In this study, we have investigated the synergistic combination between OSU-2S and sorafenib on different hepatocellular carcinoma (HCC) cell lines using cell viability, apoptosis, colony formation, invasion, migration, immunofluorescence, and western blot analysis.
Results: OSU-2S significantly synergized the anticancer activity of sorafenib as indicated by the promising combination indices. In addition, the enhanced anticancer activity was indicated by increased caspase 3/7 activation as an indicator for apoptotic cell death. This synergy was mediated through tackling many cell survival signaling pathways such as MAPK and PKC-delta.
Conclusion: OSU-2S represents a therapeutically relevant approach for treatment, and ultimately lead to new protocols that will improve the survival of cancer patients. This data might provide a promising treatment strategy for HCC.
Acknowledgment: This work was supported by a research grant number 201903 from Al Jalila Foundation.