Toxicology & Applied Pharmacology, 2016, 292:94-102.

The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

Tzu Chin Wu, Yi Chin Lin, Hsiao Ling Chen, et al

Chest Clinic, Chung Shan Medical University Hospital, Taichung, Taiwan; Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan; et al

Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation.

《毒理学和应用药理学》, 2016, 292:94-102.

金雀异黄素增强曲古菌素A对携带野生型p53基因的肺癌细胞的诱导凋亡的作用与组蛋白乙酰转移酶上调有关

吴祖钦，林逸尘，陈晓玲等

台湾台中市中山医科大学医院胸部诊所; 台湾台中市中山医科大学营养科学系; et al

已经证明染料木黄酮增强人肺癌A549细胞中曲古菌素A（TSA）的抗肿瘤活性。然而，联合治疗是否在其他肺癌细胞中发挥相同的作用尚不清楚。在本研究中，我们首先比较了染料木素对ABA-1，NCI-H460（H460）和A549细胞中TSA的抗肿瘤作用的增强作用。第二，我们调查是否染料木素的影响是与增加组蛋白/非组蛋白乙酰化相关联。我们发现染料木素对ABC-1细胞（p53突变体）细胞生长阻滞的增强作用小于A549和H460细胞。染料木黄酮增强TSA诱导A549和H460细胞而不是ABC-1细胞的凋亡。在A549和H460细胞中沉默p53表达后，染料木黄酮的增强作用减弱。此外，染料木素增加TSA诱导组蛋白H3 / H4乙酰化A549和H460细胞。染料木黄酮还增加H460细胞中的p53乙酰化。乙酰转移酶，漆树酸的抑制剂，减少染料木黄酮对所有TSA诱导的组蛋白/ p53乙酰化和凋亡的增强作用。染料木黄酮与TSA组合增加了p300蛋白（一种乙酰转移酶）在A549和NCI-H460细胞中的表达。此外，我们表明染料木素也增强了染料木素在A549肿瘤荷瘤小鼠的抗肿瘤作用。总之，这些结果表明，染料木黄酮对TSA诱导的肺癌细胞凋亡的增强作用是p53依赖性的，并且与组蛋白/非组蛋白乙酰化相关。