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Inhibition of Proliferation and Induction of Apoptosis by Thymoquinone via Modulation of TGF Family, p53, p21 and Bcl-2α in Leukemic Cells

[ Vol. 18 , Issue. 2 ]

Author(s):

Mona Diab-Assaf, Josiane Semaan, Marwan El-Sabban, Soad K. Al Jaouni, Rania Azar, Mohammad Amjad Kamal and Steve Harakeh*   Pages 210 - 215 ( 6 )

Abstract:


Introduction: Adult T-cell leukemia (ATL) is an aggressive form of malignancy caused by human T- cell lymphotropic virus 1 (HTLV-1). Currently, there is no effective treatment for ATL. Thymoquinone has been reported to have anti-cancer properties.

Objective: The aim of this study is to investigatthe effects of TQ on proliferation, apoptosis induction and the underlying mechanism of action in both HTLV-1 positive (C91-PL and HuT-102) and HTLV-1 negative (CEM and Jurkat) malignant T-lymphocytes.

Materials and methods: Cells were incubated with different thymoquinone concentrations for 24h. Cell cytotoxicity was assayed using the CytoTox 96® Non-Radioactive Cytotoxicity Assay Kit. Cell proliferation was determined using CellTiter 96® Non-Radioactive Cell Proliferation. Cell cycle analysis was performed by staining with propidium iodide. Apoptosis was assessed using cell death ELISA kit. The effect of TQ on p53, p21, Bcl-2 protein expression was determined using Western blot analysis while TGF mRNA expression was determined by RT-PCR.

Results: At non-cytotoxic concentrations of TQ, it resulted in the inhibition of proliferation in a dose dependent manner. Flow cytometric analysis revealed a shift in the cell cycle distribution to the PreG1 phase which is a marker of apoptosis. Also TQ increase DNA fragmentation. TQ mediated its anti-proliferative effect and apoptosis induction by an up-regulation of TGFβ1, p53 and p21 and a down-regulation of TGF-α and Bcl-2α.

Conclusion: Thymoquinone presents antiproliferative and proapoptotic effects in ATL cells. For this reason, further research is required to investigate its possible application in the treatment of ATL.

Keywords:

Thymoquinone, HTLV-1, ATL, TGF family, p53, p21 and Bcl-2α.

Affiliation:

Lebanese University, EDST (“Molecular Tumor-genesis and Anticancer Pharmacology”), Hadath, Lebanese University, EDST (“Molecular Tumor-genesis and Anticancer Pharmacology”), Hadath, Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Yousef Abdullatif Jameel Chair of Prophetic Medicine Application, King Abdulaziz University Hospital, Lebanese University, EDST (“Molecular Tumor-genesis and Anticancer Pharmacology”), Hadath, Yousef Abdullatif Jameel Chair of Prophetic Medicine Application, King Abdulaziz University Hospital, Yousef Abdullatif Jameel Chair of Prophetic Medicine Application, King Abdulaziz University Hospital

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