Combined effect of (-)-epigallocatechin-3-gallate and all-trans retinoic acid in flt3-mutated cell lines

Abstract

Patents diagnosed with acute promyelocytic leukemia were treated with Vesanoid® [all-trans retinoic acid (ATRA)]. ATRA promotes the maturation and differentiation of leukemia cells and is therefore capable of reducing the symp-toms of leukemia by preventing aggregation of myeloid cells. However, the clinical applications of ATRA are limited by its side effects, including acute retinoid resistance, hypertriglyc-eridemia, mucocutaneous dryness, nausea, brief recovery time relapse and drug resistance. Therefore, combinations of ATRA and other anticancer drugs are being investigated to overcome these limitations. In our previous study it was shown that in leukemia cells, (-)-epigallocatechin-3-gallate (EGCG) reduced cell proliferation and induced apoptotic cell death. In the present study, an in vitro evaluation of the effects of the combination of EGCG and ATRA on FLT3-mutated cell lines was performed using the isobologram method. The results showed that there was an additive effect in leukemic cells when treated with a combination of ATRA and EGCG. Thus, it was concluded that the cytotoxic effects of EGCG were improved by ATRA.