Effects of suberoylanilide hydroxamic acid on proliferation, cell cycle and apopto-sis of colon cancer HCT116 and SW480 cells
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Abstract:
Objective:To investigate the effects and molecular mechanisms of Suberoylanilide Hydroxamic Acid (SAHA) on the proliferation, cell cycle and apoptosis of colon cancer HCT116 and SW480 cells. Methods: Colon cancer cells (HCT116 and SW480) were treated with a series of concentrations of SAHA.MTT assay was em-ployed to evaluate the effect of SAHA on proliferation of HCT116 and SW480 cells.The cell cycle distribution and apoptosis were determined by flow cytometry.Rhodamine 123 and DCFH-DA were applied to detect the mito-chondrial membrane potential(ΔΨm) and reactive oxygen species (ROS) production.Reverse transcription poly-merase chain reaction (RT-PCR) and Western blotting were used to assess the mRNA and protein expressions of Ac-H3, p21, Cyclin D1, Bax and Bcl-2. Results: After 48 h of SAHA treatment on HCT116 and SW480 cells, the cell proliferation was inhibited,the G1 phase ratio of cells and the apoptosis rate was increased (all P<0.05); moreover,SAHA also reduced ΔΨm and increased cellular ROS production (all P<0.05). Compared with control group, the mRNA expressions of p21 and Bax were higher in SAHA group, while the mRNA expressions of CyclinD1 and Bcl-2 were lower (all P<0.05); Furthermore, the protein expressions of Ac-H3,p21 and Bax were improved,while the protein expressions of CyclinD1 and Bcl-2 were decreased in SAHA group (all P<0.05). Conclusion: SAHA may suppress cell growth, induce apoptosis and cause cell cycle arrest of colon cancer cells by promoting histone acetyla-tion and modulating their related genes of p21, CyclinD1 and Bcl-2 family.
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Project supported by the General Foundation of Science and Technology Bureau of Ed-ucation of Liaoning Provincial(No.LJQ2014333)