The present study aimed to evaluate the cytotoxicity and its mechanism of five synthetic methoxy stilbenes, namely 3,4,4'-trimethoxy, 3,4,2'-trimethoxy, 3,4,2',4'-tetramethoxy, 3,4,2',6'-tetramethoxy, and 3,4,2',4',6'-pentamethoxy-trans-stilbenes (MS), in comparison with resveratrol (RSV). Human promyelocytic (HL-60) and monocytic leukemia (THP-1) cells were treated with the tested compounds for 24 h, and cytotoxicity, cell cycle distribution, and apoptosis were evaluated. Significant differences were found in the susceptibility of these cell lines to all stilbenes, including RSV. The THP-1 cells were more resistant to cytotoxic activity of these compounds than HL-60 cells. Among the tested stilbenes, 3,4,4'-tri-MS and 3,4,2',4'-tetra-MS exhibited higher cytotoxicity toward both cell lines than RSV and the other methoxy stilbenes. This activity might be related to cell cycle arrest at the G2/M phase and induction of apoptosis. In this regard, 3,4,4'-tri-MS and 3,4,2',4'-tetra-MS at highest concentrations increased the p53 protein level particularly in HL-60 cells. Moreover, treatment with these derivatives increased the ratio of the proapoptotic Bax protein to the antiapoptotic Bcl-xl protein, suggesting the induction of apoptosis through the intrinsic mitochondrial pathway in both cell lines. Further studies are required to fully elucidate the mechanism of these activities.

中文翻译：

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白藜芦醇的类似物甲氧基对苯乙烯对人髓样白血病细胞的活力以及诱导细胞周期停滞和凋亡的作用。

本研究旨在评估5种合成的甲氧基斯蒂芬苯酯的细胞毒性及其机理，即3,4,4'-三甲氧基，3,4,2'-三甲氧基，3,4,2'，4'-四甲氧基，3，与白藜芦醇（RSV）相比，4,2'，6'-四甲氧基和3,4,2'，4'，6'-五甲氧基-反式-苯乙烯衍生物（MS）。用测试化合物处理人早幼粒细胞（HL-60）和单核细胞白血病（THP-1）细胞24小时，并评估其细胞毒性，细胞周期分布和细胞凋亡。在这些细胞系对所有斯蒂芬类药物（包括RSV）的敏感性方面发现了显着差异。与HL-60细胞相比，THP-1细胞对这些化合物的细胞毒性活性更具抵抗力。在测试的斯蒂芬酯中，3,4,4'-tri-MS和3,4,2'，4' -tetra-MS对两种细胞系的毒性均高于RSV和其他甲氧基对苯二酚。这种活性可能与细胞周期停滞在G2 / M期和诱导凋亡有关。在这方面，特别是在HL-60细胞中，最高浓度的3,4,4'-tri-MS和3,4,2'，4'-tetra-MS增加了p53蛋白水平。此外，用这些衍生物处理增加了促凋亡的Bax蛋白与抗凋亡的Bcl-xl蛋白的比率，表明通过两种细胞系中固有的线粒体途径诱导凋亡。需要进一步研究以充分阐明这些活动的机制。最高浓度的-tetra-MS可增加p53蛋白水平，尤其是在HL-60细胞中。而且，用这些衍生物处理增加了促凋亡的Bax蛋白与抗凋亡的Bcl-xl蛋白的比率，表明通过两种细胞系中固有的线粒体途径诱导凋亡。需要进一步研究以充分阐明这些活动的机制。最高浓度的-tetra-MS可增加p53蛋白水平，尤其是在HL-60细胞中。此外，用这些衍生物处理增加了促凋亡的Bax蛋白与抗凋亡的Bcl-xl蛋白的比率，表明通过两种细胞系中固有的线粒体途径诱导凋亡。需要进一步研究以充分阐明这些活动的机制。