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Abstract：
Cancer is one of the most important problems of modern societies. Recently, studies have reported the anticancer properties of rosiglitazone related to its ability to bind peroxisome proliferator receptor γ (PPARγ), which has various effects on cancer and can inhibit cell proliferation. In this study, we investigated the effect of new 4-thiazolidinone (4-TZD) hybrids Les-4369 and Les-3467 and their effect on reactive oxygen species (ROS) production, metabolic activity, lactate dehydrogenase (LDH) release, caspase-3 activity, and gene and protein expression in human foreskin fibroblast (BJ) cells and lung adenocarcinoma (A549) cells. The ROS production and caspase-3 activity were mainly increased in the micromolar concentrations of the studied compounds in both cell lines. Les-3467 and Les-4369 increased the mRNA expression of PPARG, P53 (tumor protein P53), and ATM (ATM serine/threonine kinase) in the BJ cells, while the mRNA expression of these genes (except PPARG) was mainly decreased in the A549 cells treated with both of the tested compounds. Our results indicate a decrease in the protein expression of AhR, PPARγ, and PARP-1 in the BJ cells exposed to 1 µM Les-3467 and Les-4369. In the A549 cells, the protein expression of AhR, PPARγ, and PARP-1 increased in the treatment with 1 µM Les-3467 and Les-4369. We have also shown the PPARγ modulatory properties of Les-3467 and Les-4369. However, both compounds prove weak anticancer properties evidenced by their action at high concentrations and non-selective effects against BJ and A549 cells.
摘要：
癌症是现代社会最重要的问题之一。最近,研究报道了罗格列酮的抗癌特性与其结合过氧化物酶体增殖物受体γ（PPARγ）的能力有关，对癌症有多种作用，并能抑制细胞增殖。在这项研究中,我们研究了新的4-噻唑烷酮（4-TZD）杂种Les-4369和Les-3467的影响及其对活性氧（ROS）产生的影响，代谢活动，乳酸脱氢酶（LDH）释放，caspase-3活性，在人包皮成纤维细胞（BJ）细胞和肺腺癌（A549）细胞中的基因和蛋白表达。在两种细胞系中，所研究化合物的微摩尔浓度主要增加了ROS的产生和caspase-3的活性。Les-3467和Les-4369增加PPARG的mRNA表达,P53（肿瘤蛋白P53），和ATM（ATM丝氨酸/苏氨酸激酶）在BJ细胞，而用两种测试化合物处理的A549细胞中这些基因(PPARG除外)的mRNA表达主要降低。我们的结果表明AhR的蛋白质表达减少，PPARγ,和暴露于1µMLes-3467和Les-4369的BJ细胞中的PARP-1。在A549细胞中,AhR的蛋白表达，PPARγ,在1µMLes-3467和Les-4369的治疗中，PARP-1增加。我们还显示了Les-3467和Les-4369的PPARγ调节特性。然而,这两种化合物都证明了弱的抗癌特性,这通过它们在高浓度下的作用和对BJ和A549细胞的非选择性作用来证明。
