Abstract
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.