Molecular investigation of therapeutical effects of Ɣ-tocotrienol conjugation therapy with doxorubicin on hepatocellular carcinoma cell line HePG2

Özyurt, İpek
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.


Regulation of Glutathione S-Transferase Mu with type 1 diabetes and its regulation with antioxidants
SADİ, GÖKHAN; Kartal, Deniz Irtem; Güray, Nülüfer Tülün (2013-01-01)
Objective: Increased oxidative stress is now related with the pathogenesis and the chronic complications associated with the disease, diabetes mellitus. While roles of oxidative stress in diabetic complications are widely studied, the molecular mechanisms playing role in the regulations of detoxification enzymes in the presence of antioxidants have not been clearly established because of the complexity of the pathways.
Karaciğer kanseri kök hücre ksenograft modelinde sitotoksik aktiviteli yeni ilaç adaylarının etkilerinin belirlenmesi
Atalay, Rengül; Kahraman, Deniz Cansen(2017)
Primer karaciğer kanseri (Hepatoselüler kanser, HSK) Dünya sağlık örgütü verilerine göre altıncı en sık görülen ve diğer kanser türleri arasında ölümcül olan ikinci kanser türüdür. Karaciğer kanserinin histolojik yapısı oldukça heterojendir. Sıklıkla siroz zemininde oluşan karaciğer kanseri, hepatik öncü hücre (Hepatic Progenitor Cells HPC) olarak adlandırılan hücrelerden kaynaklanmaktadır. Kök hücre belirteçlerini ve özelliklerini taşıyan bu hücreler, kronik hepatit ve siroz sürecinde uzun süreli hasara uğ...
Identification of gene mutations involved in drug resistance in liver cancer using RNA-SEQ data analysis
Shojaei, Mona; Atalay, Rengül; Acar, Aybar Can; Department of Bioinformatics (2016)
A significant concern in cancer research is the detection of cancer associated somatic mutations. Liver cancer is the 5th most common and 2nd deadliest cancer in the world. Several somatic mutations were previously reported in liver cancer but their relations to chemotherapeutic response was not studied in detail. In this study, the relationship between mutation status and drug treatment response of well-differentiated Huh7 and poorly-differentiated Mahlavu liver cancer cells were analyzed. The RNA-Seq data...
Capture and release of viable CTCs in microfluidic channel
Ateş, Hatice Ceren; Şen Doğan, Begüm; Özgür, Ebru; Külah, Haluk (null; 2017-10-04)
The number of circulating tumor cells (CTCs) in blood is associated with prognosis in several types of cancer. Isolation and characterization of CTCs have important clinical significance in terms of prognosis and early detection of response to treatment. Moreover, downstream characterization of CTCs may help better patient stratification and therapy guidance. However, CTCs are extremely rare and highly sensitive and specific technology is required to isolate viable CTCs from blood cells. In this study, a su...
Structural effects of simvastatin on liver rate tissue: Fourier transform infrared and Raman microspectroscopic studies
Garip, Sebnem; Bayari, Sevgi Haman; Severcan, Mete; Abbas, Sherif; Lednev, Igor K.; Severcan, Feride (2016-02-01)
Simvastatin is one of the most frequently prescribed statins because of its efficacy in the treatment of hypercholesterolemia, reducing cardiovascular risk and related mortality. Determination of its side effects on different tissues is mandatory to improve safe use of this drug. In the present study, the effects of simvastatin on molecular composition and structure of healthy rat livers were investigated by Fourier transform infrared and Raman imaging. Simvastatin-treated groups received 50 mg/kg/day simva...
Citation Formats
İ. Özyurt, “Molecular investigation of therapeutical effects of Ɣ-tocotrienol conjugation therapy with doxorubicin on hepatocellular carcinoma cell line HePG2,” M.S. - Master of Science, Middle East Technical University, 2017.