The effects of Epigallocatechin-3-gallate and Dabrafenib combination on apoptosis and the genes involved in epigenetic events in anaplastic thyroid cancer cells.

ABSTRACT

Anaplastic thyroid cancer cases with poor prognosis are associated with epigenetic modifications such as abnormal DNA methylation. Epigallocathesin-3-gallate (EGCG) is a polyphenol compound of green tea that is still under investigation on its role in cancer prevention. EGCG is known as an epigenetic diet in DNA methyltransferase inhibitor. The cytotoxic effects of Dabrafenib, EGCG, and dabrafenib in combination with EGCG were assessed by using WST-8 assay; and also, Flow cytometry was utilized to identify cells undergoing apoptosis after treatments of the SW-1736 cells. We investigated the mRNA expression of genes involved in epigenetic events in SW-1736 cells by real-time qRT-PCR following the treatments. We demonstrated for the first time that the Dabrafenib-EGCG combination reduced cell viability significantly depending on concentration and induced apoptosis by 8.49-fold through investigating the additive effect together on SW-1736 cells. The IC50 doses of Dabrafenib and EGCG for 48 h were determined as 6.7 µM and 22.5 µM, respectively. The results of qRT-PCR demonstrated that the Dabrafenib-EGCG combination significantly caused the down-regulation of genes involved in epigenetic regulation. We suggest that the combination of Dabrafenib and EGCG following in vivo phase studies will contribute as an alternative treatment option for the treatment of ATC.