金雀异黄素和 β-胡萝卜素可以在 A549 细胞中促进曲古菌素 A的生长抑制作用_肖荣仁

针对病种：肺癌

发表时间：2010年2月

发表国家：德国

登载刊物：欧洲营养学报

研究单位：台湾建国科技大学美容科，台湾弘光科技大学食物和营养学院等

研究人员：肖荣仁，陈启勇等

主要结论：金雀异黄素和 β-胡萝卜素能够增强 TSA 对 A549 细胞的生长抑制作用。金雀异黄素至少部分通过增加半胱氨酸蛋白酶-3 的活性来发挥作用，而 β-胡萝卜素可能主要通过半胱氨酸蛋白酶-3-独立通路来促进TSA 诱导细胞死亡.

European Journal of Nutrition, 2010, 49(1):19-25.

Genistein and β-carotene enhance the growth-inhibitory effect of trichostatin A in A549 cells

Rong Jen Shiau, Kai Yong Chen, et al

Department of Beauty Science, Chienkao Technology University, Changhua, Taiwan, ROC; Department of Food and Nutrition, Hungkuang University, Taichung County, Taiwan, ROC; et al

Background: The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy and decreasing the toxicity of chemotherapy. However, whether nutritional factors enhance the effect of trichostatin A (TSA), a novel anti-cancer drug, is unclear.

Aim: We investigated the individual enhancing effect and its possible mechanisms of genistein, daidzein, β-carotene, retinoic acid, and α-tocopherol on the cell-growth-inhibitory effect of TSA in a human lung carcinoma cell line, A549.

Methods: A549 cells were incubated with TSA (50 mg/mL) alone or in combination with the various nutritional factors for various times, and cell growth was measured. IMR90 cells, human lung fibroblasts, were also incubated with TSA alone or in combination with genistein or β-carotene to determine the selectivity of these treatments. In addition, we studied effects on the cell cycle, caspase-3 activity, and DNA damage (by comet assay) in A549 cells.

Results: After treatment for 72 h, 10-μM genistein or β-carotene significantly enhanced the growth-inhibitory effect of TSA in A549 cells. Daidzein, retinoic acid, and α-tocopherol at the same concentration had no significant effect. However, genistein and β-carotene failed to enhance the cell-growth-arrest effect of TSA in IMR90 cells. Flow cytometric analysis showed that both genistein and β-carotene significantly increased the TSA-induced apoptosis in A549 cells. Genistein significantly enhanced TSA-induced caspase-3 activity in A549 cells by 34% at 24 h, and the caspase-3 inhibitor partly inhibited the enhancing effect of genistein on TSA-induced apoptosis. β-Carotene did not significantly affect TSA-induced caspase-3 activity. However, β-carotene rather than genistein enhanced TSA-induced DNA damage.

Conclusions: Genistein and β-carotene enhance the cell-growth-arrest effect of TSA on A549 cells. Genistein exerts its effect, at least partly, by increasing caspase-3 activity; whereas β-carotene may enhance TSA-induced cell death mainly through a caspase-3-independent pathway.

德国《欧洲营养学报》2010年2月

金雀异黄素和 β-胡萝卜素可以在 A549 细胞中促进曲古菌素 A的生长抑制作用

肖荣仁，陈启勇等

台湾建国科技大学美容科，台湾弘光科技大学食物和营养学院等

背景︰抗肿瘤药物与营养因素结合是一种潜在的提高疗效，降低化疗毒性的方法。然而，营养因素是否能提高曲古霉素 (TSA)这种新型抗癌药物的疗效尚不清楚。

目的︰我们分别探究了染料木素、大豆黄酮、 β-胡萝卜素、视黄酸和 α-生育酚各自对 TSA 在人类肺癌细胞系A549 细胞中的生长抑制作用及其可能机制。

方法︰单独在TSA（50 mg/mL）中或者结合各种营养因素在不同的时间段孵育A549 细胞，测试细胞生长情况。同样在TSA中单独或结合金雀异黄酮或 β-胡萝卜素孵育人体肺成纤维细胞IMR90来确定这些治疗方法的选择性。此外，我们还研究了在A549 细胞中它们对细胞周期、半胱氨酸蛋白酶-3 的活性和DNA 损伤（通过彗星实验）的影响。

结果︰在治疗 72 小时后，10 μ M的金雀异黄素或 β-胡萝卜素明显增强了TSA 对A549 细胞的生长抑制作用。相同浓度下大豆黄酮、视黄酸和 α-生育酚却没有显著的影响。然而，金雀异黄素和 β-胡萝卜素未能增强 TSA对IMR90 细胞的生长抑制作用。流式细胞术的分析表明金雀异黄素和 β-胡萝卜素能够显著增加 TSA 诱导 A549 细胞凋亡的作用。金雀异黄素在 24 h时显著增强了 TSA 诱导 A549 细胞的半胱氨酸蛋白酶-3 的活性 34%，并且半胱氨酸蛋白酶-3 抑制剂部分抑制了金雀异黄素对 TSA 诱导凋亡的促进作用。β-胡萝卜素没有显著影响 TSA对半胱氨酸蛋白酶-3 活性的诱导。然而，β-胡萝卜素比金雀异黄素更能增强 TSA 对DNA 损伤的诱导作用。

结论︰金雀异黄素和 β-胡萝卜素能够增强 TSA 对 A549 细胞的生长抑制作用。金雀异黄素至少部分通过增加半胱氨酸蛋白酶-3 的活性来发挥作用，而 β-胡萝卜素可能主要通过半胱氨酸蛋白酶-3-独立通路来促进TSA 诱导细胞死亡。