EVALUATING THE THERAPEUTIC POTENTIAL OF CROCIN AGAINST DIETHYLNITROSAMINE INDUCED EXPERIMENTAL HEPATOCELLULAR CARCINOMA IN RATS

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the third cause of cancer-related death worldwide. Liver cancer is the result of repeated injuries to the liver triggered by different causes. Currently, sorafenib is the only drug U.S. Food and Drug Administration approved targeted therapy. Sorafenib, an oral multikinase inhibitor, which inhibits the proliferation of tumor cells and blocks angiogenesis. Sorafenib has been shown to treat early and mild HCC lesions and it helped increase the survival rates at one year, but for only 44% of patients. Chemotherapies are an important line of defense when it comes to cancer. HCC, however, is been proven to be chemo-resistant and the side effects of chemotherapies lower the quality of life for cancer patients due to their non-selective cytotoxicity. Thus, the search for better HCC treatment options is essential. A carcinogenesis model that mimics the human disease was developed here to test the effects of crocin, one of the major bioactive molecules found in saffron. Crocin is a natural compound with strong-anti-oxidant, hepatoprotective, and anti-inflammatory effects. Crocin has been shown to kill different cancers in vitro. In this study and compared to monotherapy, combination therapy (crocin + sorafenib) simultaneously targeted multiple pathways and provided a better treatment option. The effects of crocin were investigated on DEN-induced HCC in male Wistar rats. Crocin has been found to be involved in the mitochondrial, apoptotic pathway triggering cell death and tumor suppression. This study highlights crocin’s therapeutic effects against HCC both as a single agent and in combination with sorafenib