Diab-Assaf Mona, Semaan Josiane, El-Sabban Marwan, Al Jaouni Soad K, Azar Rania, Kamal Mohammad Amjad, Harakeh Steve
Lebanese University, EDST ("Molecular Tumor-genesis and Anticancer Pharmacology"), Hadath, Lebanon.
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Anticancer Agents Med Chem. 2018;18(2):210-215. doi: 10.2174/1871520617666170912133054.
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.
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.
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.
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.
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.
成人T细胞白血病（ATL）是由人类T细胞嗜淋巴细胞病毒1型（HTLV-1）引起的侵袭性恶性肿瘤形式。目前，尚无针对ATL的有效治疗方法。据报道，百里醌具有抗癌特性。
本研究旨在调查百里醌（TQ）对HTLV-1阳性（C91-PL和HuT-102）和HTLV-1阴性（CEM和Jurkat）恶性T淋巴细胞的增殖、凋亡诱导作用及其潜在作用机制。
将细胞与不同浓度的百里醌孵育24小时。使用CytoTox 96®非放射性细胞毒性检测试剂盒检测细胞毒性。使用CellTiter 96®非放射性细胞增殖检测法测定细胞增殖。通过碘化丙啶染色进行细胞周期分析。使用细胞死亡ELISA试剂盒评估凋亡。使用蛋白质免疫印迹分析确定TQ对p53、p21、Bcl-2蛋白表达的影响，同时通过逆转录聚合酶链反应（RT-PCR）确定TGF mRNA表达。
在TQ的非细胞毒性浓度下，它以剂量依赖方式导致增殖抑制。流式细胞术分析显示细胞周期分布向PreG1期转变，这是凋亡的一个标志。此外，TQ增加DNA片段化。TQ通过上调TGFβ1、p53和p21以及下调TGF-α和Bcl-2α介导其抗增殖作用和凋亡诱导。
百里醌在ATL细胞中呈现抗增殖和促凋亡作用。因此，需要进一步研究以调查其在ATL治疗中的可能应用。
