Effect of Curcumin on SMCT-1 Expression and Dichloroacetate Toxicity in HCT116 Colon Cancer Cells

Background: Colorectal cancer is a common cause of cancer-related deaths Epigenetic regulation of the influx sodium dependent monocarboxylate transporter-1 )SMCT1), a tumor suppressor, was recognized in colorectal cancer. In this study, effects of Curcumin (Cur), on SMCT1 gene expression was determined. A low SMCT1 expression, HCT116, cell line was used to test an in vitro effect of Cur on epigenetic regulation of SMCT1 expression via DNA methylation and its function. It was hypothesized that Cur can induce SMCT1 expression in the cells via hypomethylation effect. Measurement of increase in SMCT1 function was performed using dichloroacetate (DCA), a cytotoxic substrate of SMCT1.

Methods: The effect of 5′Azacytidine (Aza), a hypomethylating agent, and Cur on SMCT1 expression and function was determined. Cells were treated with Aza and various concentrations of Cur for 72 h. After that SMCT1 expression was determined by real time PCR and Western blotting. To evaluate the SMCT1 function, DCA was used in MTT assay.

Results: After treatment with 40 µM Cur, SMCT1 mRNA was significantly increased (p < 0.05). This was correlated with SMCT1 protein expression. Cells treated with 40 µM of Cur showed significant increase of cytotoxicity at DCA concentrations of 25 (p < 0.001) and 12.5 mM (p <0.01), respectively.

Conclusion: Cur was shown to significantly induce the SMCT1 mRNA and protein expression in HCT116 cells. The induction of the SMCT1 protein increased DCA cytotoxicity, presumably through an increase of DCA transport into the cells. The mechanism underlying of SMCT1 induction by Cur may result from not only hypomethylation but other epigenetics.