In vitro analysis of synergistic anti-cancer effects of Sorafenib and Cynara scolymus L. leaf extract on hepatocellular carcinoma

According to the 2020 data of the World Health Organization, primary liver cancer is the fifth most common cancer worldwide and the second leading cause of cancer mortality. Hepatocellular carcinoma is the most common histologic type of primary liver cancer and it accounts for between 85% and 90% of these malignancies. The overall prognosis of patients with liver cancer is poor (ratio of mortality to incidence 0.95). Systemic chemotherapy remains the mainstay of therapy for patients with advanced HCC who are not candidates for surgical resection, liver transplantation, or localized tumor ablation. Approved by the US Food and Drug Administration in 2005, Sorafenib is a multiple tyrosine kinase inhibitor that was used in the treatment of hepatocellular carcinoma in 2007. It has become widespread for healthcare professionals to use alternative medicine techniques during treatment for all cancer types. Patients who continue their treatment are using the extracts of many plant species or their active ingredients under supervision or uncontrolled to reduce the side effects of the drugs or to support the treatment. Cynara scolymus (Artichoke) is a plant species belonging to the Asteraceae family, containing the active ingredient cynarin. Cynara scolymus, which is widely used in people with liver diseases, is used by liver cancer patients to reduce the side effects of chemotherapy. The combination effect of Sorafenib and Cynara scolymus L. leaf extract used in the treatment of hepatocellular carcinoma was investigated within the scope of the thesis. Anti-cancer and anti-proliferative synergistic effect of different concentration combinations of Sorafenib and Cynara scolymus L. leaf extract on hepatocellular carcinoma cell line (HepG2); cell viability test (XTT), determination of expression levels of some genes (TNF-α, Bax, Caspase 3 and Bcl2) by RT-qPCR method and determination of protein levels of the same genes by ELISA method. In addition, biochemical evaluations were made by measuring the activities of Catalase, Carbonic anhydrase and Glutathione peroxidase enzymes.