Ethacrynic acid and a derivative enhance apoptosis in arsenic trioxide-treated myeloid leukemia and lymphoma cells: the role of glutathione S-transferase p1-1.

ABSTRACT:

Purpose

Arsenic trioxide (ATO) as a single agent is used for treatment of acute promyelocytic leukemia (APL) with minimal toxicity, but therapeutic effect of ATO in other types of malignancies has not been achieved. We tested whether a combination with ethacrynic acid (EA), a glutathione S-transferase P1-1 (GSTP1-1) inhibitor, and a reactive oxygen species (ROS) inducer will extend the therapeutic effect of ATO beyond APL.

Experimental design

The combined apoptotic effects of ATO plus ethacrynic acid were tested in non-APL leukemia and lymphoma cell lines. The role of ROS, GSTP1-1, glutathione (GSH), and Mcl-1 in apoptosis was determined. The selective response to this combination of cells with and without GSTP1-1 expression was compared.

Results

ATO/EA combination sy

SUBMITTER: Wang R 

PROVIDER: S-EPMC3525753 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature