Molecular investigation of therapeutical effects of ɣ tocotrienol conjugation therapy with doxorubicin on hepatocellular carcinoma cell line HEPG2

Thesis Type: Postgraduate

Institution Of The Thesis: Middle East Technical University, Graduate School of Natural and Applied Sciences, Biology, Turkey

Approval Date: 2017

Thesis Language: English


Consultant: Çağdaş Devrim Son


Hepatocellular carcinoma (HCC) is the fifth leading tumor of the liver tissue in terms of frequency of occurrence and third in terms of mortality. Even though, the most widely used chemotherapeutic agent doxorubicin in treatment of HCC had a great impact for development of therapeutic strategies preventing the progression of tumor formation and elucidating the physiological characteristics of tumor tissue. Moreover, use of doxorubicin minimizes the side effects of the drug in the individual and prevents the resistance developed by the HCC cells. However, vitamin E derivatives, especially γ-tocotrienol rich fractions have an anti-proliferative and inhibitory effect on cancer cells by several means, including evading the gained resistance of HCC cells to chemotherapic agents and inducing apoptosis. Furthermore, when cells were cotreated with γ-tocotrienol and chemotherapy drugs, synergistic effect was observed. In this study It has been shown that the combination of doxorubicin chemotherapeutic agent with γ-tocotrienol, which belongs to Vitamin E family of molecules, causes changes in the molecular mechanism of liver cancer cells and lipid metabolism. In this study, we have shown that these changes are caused not only by reducing the side effects caused by doxorubicin, but also by reversing the resistance of HCC cells for the actions of chemotherapeutic agents.