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. 2020 Oct;13(4):25.
doi: 10.3892/br.2020.1332. Epub 2020 Jul 22.

Combined effect of (-)-epigallocatechin-3-gallate and all-trans retinoic acid in FLT3-mutated cell lines

Bui Thi Kim Ly  1   2 , Hoang Thanh Chi  3   4
Affiliations

Combined effect of (-)-epigallocatechin-3-gallate and all-trans retinoic acid in FLT3-mutated cell lines

Bui Thi Kim Ly et al. Biomed Rep. 2020 Oct.

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 symptoms of leukemia by preventing aggregation of myeloid cells. However, the clinical applications of ATRA are limited by its side effects, including acute retinoid resistance, hypertriglyceridemia, 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.

Keywords: ATRA; EGCG; green tea; isobologram; leukemia.

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Figures

Figure 1
Figure 1
Isobolographs of simultaneous treatment with ATRA and EGCG. Isobolographs of the various treatments in (A) MOLM-13, (B) KOCL-48, (C) MV4-11 and (D) MOLM-14 cells. Each data point represents the mean ± standard deviation of at least three separate experiments in isobolograms. Treatment with a combination of ATRA and EGCG had an additive effect on MOLM-13 cells and an antagonistic effect on MOLM-14, MV4-11 and KOCL-48 cells. ATRA, all-trans retinoic acid; EGCG, (-)-epigallocatechin-3-gallate.
Figure 2
Figure 2
Comparison of the predicted maximum data for an additive effect with the observed data obtained from simultaneous exposure to all-trans retinoic acid and (-)-epigallocatechin-3-gallate. Predicted max and observed effects of combined treatment in (A) KOCL-18, (B) MV4-11 and (C) MOLM-14 cells.
See this image and copyright information in PMC

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