Sensitization to γ-irradiation-induced cell cycle arrest and apoptosis by the histone deacetylase inhibitor trichostatin A in non-small cell lung cancer (NSCLC) cells

Histone deacetylase (HDAC) inhibitors (HDIs) play an important role in the regulation of gene expression associated with cell cycle and apoptosis and have emerged as promising anticancer agents. In addition to their intrinsic anticancer properties, some studies have demonstrated that HDIs can modulate cellular responses to ionizing radiation (IR). Here we show evidence that co-treatment with the HDI trichostatin A (TSA) radiosensitizes human non-small cell lung cancer (NSCLC) A549 cells and H1650 cells. Cells were exposed to γ-irradiation with or without TSA co-treatment. Clonogenic survival was significantly reduced in cells with TSA co-treatment. In A549 cells, TSA enhanced IR-induced accumulation of cells in G2/M phase, with upregulated expression of P21waf1/cip1. In addition, TSA co-treatment caused pronounced apoptosis in irradiated cells, which was accompanied with P21waf1/cip1 cleavage to a 15 kDa protein. The enhanced apoptotic effect was via mitochondrial pathway, as indicated by the increased di...