With the improvement and advance in cancer diagnosis and treatment, the cancer is still a major cause of morbidity and mortality throughout the world. Obviously, new breakthroughs in therapies remain be urgent needed. In this work, we designed and synthesized the compound 1-4, namely resveratrol analogues with methylation of hydroxy distyrene, to further explore its new anti-cancer potential. Encouragingly, compound 1 ((E)-4,4'-(ethene-1,2-diyl)bis(3,5-dimethylphenol)) exhibited cytotoxicity superior to resveratrol in MCF 7 cells. More importantly, the compound 1 showed greater toxicity to tumor cells than that to normal cells, which proved that it could selectively kill tumor cells. The favorable results encouraged us to explore the inhibitory mechanism of compound 1 on MCF 7 cells. The research finding indicated the compound 1 inhibited tumor cell proliferation by both arresting cell cycle in S phase and apoptosis via a prooxidant manner. In addition, the results further verified compound 1 caused cell cycle arrest in S phase and apoptosis by down-regulation of the cycling A1/cycling A2 expression and the rise of Bax/Bcl-2 ratio in a p21-dependant pathway in MCF 7 cells. Therefore, these results are helpful for the effective design of anticancer reagents and the better understanding of their mechanism of action.

中文翻译：

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寻找一种有效的白藜芦醇类似物的四甲基化羟基二乙烯作为潜在的抗癌药。

随着癌症诊断和治疗的改善和进步，癌症仍然是全世界发病率和死亡率的主要原因。显然，仍然迫切需要疗法的新突破。在这项工作中，我们设计并合成了化合物1-4，即具有羟基二苯乙烯甲基化的白藜芦醇类似物，以进一步探索其新的抗癌潜力。令人鼓舞的是，化合物1（（E）-4,4'-（乙烯-1,2-二基）双（3,5-二甲基苯酚））在MCF 7细胞中表现出优于白藜芦醇的细胞毒性。更重要的是，化合物1对肿瘤细胞的毒性大于对正常细胞的毒性，这证明它可以选择性杀死肿瘤细胞。良好的结果鼓励我们探索化合物1对MCF 7细胞的抑制机制。研究发现表明，化合物1通过阻止细胞在S期的周期和通过促氧化剂的凋亡来抑制肿瘤细胞的增殖。此外，该结果进一步证实了化合物1通过下调循环周期A1 /循环A2的表达以及MCF 7细胞中p21依赖性途径中Bax / Bcl-2比的升高而引起了S期细胞周期停滞和凋亡。 。因此，这些结果有助于抗癌试剂的有效设计和更好地了解其作用机理。该结果进一步证实了化合物1通过下调循环周期A1 /循环A2的表达以及MCF 7细胞中p21依赖性途径中Bax / Bcl-2比的升高而导致了S期细胞周期停滞和凋亡。因此，这些结果有助于抗癌试剂的有效设计和更好地了解其作用机理。该结果进一步证实了化合物1通过下调循环周期A1 /循环A2的表达以及MCF 7细胞中p21依赖性途径中Bax / Bcl-2比的升高而导致了S期细胞周期停滞和凋亡。因此，这些结果有助于抗癌试剂的有效设计和更好地了解其作用机理。