Abstract
Abstract
Introduction: Adult T-cell leukemia (ATL) is caused by human T-cell lymphotropic virus 1 (HTLV-1) and is an aggressive form of malignancy. So far, there is no effective treatment for ATL. Thymoquinone has been reported to exhibit many useful effects including anti-cancerous properties. Objective: The aim of this study is to investigated the 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 treated with various concentrations of thymoquinone 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 using 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 inhibition of proliferation in a dose dependant manner. Flow cytometric analysis revealed a shift in the cell cycle distribution to the PreG1 phase which is a marker of apoptosis. Also TQ increased 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 showed antiproliferative and proapoptotic potentials in ATL cells. For this reason, further research is required to investigate its possible application in the treatment of ATL.
Citation Format: Steve Harakeh, Josiane Semaan, Marwan El Sabban, Soad K. Al Jaouni, Mona Diab-Assaf, Rania Azar. Thymoquinone Inhibits Proliferation and induces apoptosis in leukemic cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4300. doi:10.1158/1538-7445.AM2017-4300