The Combination Effect of Sodium Butyrate, 5-aza-2'-deoxycytidine on the Tumor Suppressive Activity in RKO Colorectal Cancer and MCF-7 Breast Cancer Cell Lines

ABSTRACT

PURPOSE: It is known that DNA methylation is associated with histone acetylation status in regulation of gene expression. In this study, we investigate the effect of demethylating agents and histone deacetylase (HDAC) inhibitor on the tumor suppression and the combined effect of two agents according to methylation status in human colon and breast cancer cell lines. METHODS: In this study, the RKO colorectal cancer cell line, MCF-7 breast cancer cell lines were considered. For each cell line, we used HDAC inhibitor sodium butyrate (SB), demethylating agent 5-aza-2'-deoxycytidine (5-aza-DC) and a combination of both agents. We estimated the percentage of cell survival using the XTT method and experimented with the augmentative effects of both agents. RESULTS: In RKO cell line in which most of the genes are methylated, 74% of cell survival was shown for 5-aza-DC treatment and 83% of cell survival for SB treatment. In MCF-7 cell line that approximately half of the genes are methylated, 82% cell survival was shown for 5-aza-DC treatment and 63% cell survival for SB treatment. We observed that the survival fraction is lower after the combined treatment of 5-aza-DC and SB than that of 5-aza-DC or SB alone in both RKO (53%) and MCF-7 (49%) cell lines (P<0.001). CONCLUSION: For highly methylated genes, 5-aza-DC is more effective on the tumor suppression than SB. On the other hand, if the methylation of the promoter region is at low density, SB is noted to be more effective than 5-aza-DC. Furthermore, the combined treatment of 5-aza-DC and SB is more effective than using each agent alone.