Antitumoral effect of Ocoxin in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is becoming one of the most prevalent types of cancer worldwide. The most efficient types of treatment at present include surgical resection and liver transplantation, but these treatments may only be used in a small percentage of patients. In order to identify novel therapeutic strategies for this disease, the present study explored the potential antitumoral effect of Ocoxin® oral solution (OOS) in HCC. OOS inhibited the proliferation of HCC cell lines in a time-and dose-dependent manner, being more efficient when used in combination with sorafenib, a standard of care treatment for patients diagnosed with advanced-stage disease. Mechanistic studies indicated that the effect of OOS was due to the induction of cell cycle arrest rather than the stimulation of apoptotic cell death. The cell cycle was slowed down in all phases in the HCC cell lines treated with OOS. Finally, when tested in animal models of HCC, OOS reduced tumor progression through the induction of necrosis in xenograft tumor models. Considering the poor prognosis and high resistance to antitumor treatments of HCC, the antiproliferative action of OOS, particularly in combination with sorafenib, provides the opportunity to investigate the effect of combined therapy in a clinical setting.The present study was supported by Catalysis S.L. and the Ministry of Economy and Competitiveness of Spain (grant no., BFU2012-39151). The present study was supported by a contract from the Spanish Cancer Network (grant no. AECC12/GC02). The Institute of Molecular and Cellular Cancer Biology (CSIC-University of Salamanca) laboratory received support from the European Community through the regional development funding program and from the Fundación Ramón Areces.Peer Reviewe