Phenethyl isothiocyanate and paclitaxel synergistically enhanced apoptosis and alpha-tubulin hyperacetylation in breast cancer cells.
Phenethyl isothiocyanate and paclitaxel synergistically enhanced apoptosis and alpha-tubulin hyperacetylation in breast cancer cells.
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DOI：
10.1186/2162-3619-3-5
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发表时间：
2014-02-05
影响因子：
10.9
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Cang S;Ma Y;Chiao JW;Liu D
苯乙基异硫氰酸酯（PEITC）和紫杉醇（紫杉醇）的组合已被证明协同工作，以增加乳腺癌细胞的凋亡和细胞周期停滞。在本报告中，我们进一步探讨了PEITC和紫杉醇在MCF 7和MDA-MB-231（MB）乳腺癌细胞系中协同活性的机制。通过蛋白质印迹分析，用PEITC和紫杉醇两者处理MCF 7细胞导致α-微管蛋白的特异性乙酰化分别比单一试剂PEITC和紫杉醇增加10.4倍和5.96倍。在MB细胞中也观察到对α-微管蛋白乙酰化的这种协同作用。PEITC和紫杉醇联合应用还降低了细胞周期调节因子Cdk 1和抗凋亡蛋白bcl-2的表达，增强了Bax的表达和PARP蛋白的切割。本研究为表观遗传学药物PEITC与化疗药物紫杉醇之间的协同作用机制提供了生化证据。
Combination of phenethyl isothiocyanate (PEITC) and paclitaxel (taxol) has been shown to work synergistically to increase apoptosis and cell cycle arrest in breast cancer cells. In this report, we further explored the mechanisms for the synergistic activity of PEITC and taxol in MCF7 and MDA-MB-231 (MB) breast cancer cell lines. By Western blotting analysis, treatment of MCF7 cells with both PEITC and taxol led to a 10.4-fold and 5.96-fold increase in specific acetylation of alpha-tubulin over single agent PEITC and taxol, respectively. This synergistic effect on acetylation of alpha-tubulin was also seen in MB cells. The combination of PEITC and taxol also reduced expressions of cell cycle regulator Cdk1, and anti-apoptotic protein bcl-2, enhanced expression of Bax and cleavage of PARP proteins. In conclusion, this study provided biochemical evidence for the mechanism of synergistic effect between the epigenetic agent PEITC and the chemotherapeutic agent taxol.