Background: Head-and-neck squamous cell carcinoma is associated with the epigenetic silencing of various genes such as DAPK, ataxia telangiectasia mutated (ATM), BRCA1, p16INK4a, pVHL, p16, and RASSF1A. The most common epigenetic change observed in these genes is DNA methylation that directs the studies toward finding inhibitors for DNA methyltransferases (DNMTs), the protagonist in the action. The present study focuses on analyzing the possibility whether indole curcumin can reverse epigenetic changes of the various tumor suppressor genes, characteristically silenced by methylation, by inhibiting the major methylation enzyme DNA methyltransferase 1 or DNMT1.
Materials and methods: The cytotoxic effects of indole curcumin were studied through the MTT and lactate dehydrogenase assays. To determine the apoptosis-mediated death of HEp-2 cells, fluorescence imaging using different stains was done. Gene or mRNA expression analysis was done for p53, ATM, and DAPK genes.
Results: The results obtained from this study clearly indicate that the indole analog of curcumin plays a remarkable role in activating genes involved in cell cycle regulation and apoptosis induction through epigenetic regulation. The influence that the drug has on the methylation status of gene promoter sequence of the ATM gene is also very significant.
Conclusion: Indole curcumin, being an analog of curcumin, promises to be a very useful drug molecule having various potential targets. The target selected for this study was DNMT1 enzyme and the drug seems to actually show the effects; it was predicted to be having on the target molecule.
Keywords: Ataxia telangiectasia mutated; DNA methyltransferase; epigenetics; indole curcumin analog; tumor suppressor genes.