Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells.

ABSTRACT:

Background

Standard therapy for acute promyelocytic leukaemia (APL) includes retinoic acid (all-trans retinoic acid (ATRA)), which promotes differentiation of promyelocytic blasts. Although co-administration of arsenic trioxide (ATO) with ATRA has emerged as an effective option to treat APL, the molecular basis of this effect remains unclear.

Methods

Four leukaemia cancer human models (HL60, THP-1, NBR4 and NBR4-R2 cells) were treated either with ATO alone or ATO plus ATRA. Cancer cell survival was monitored by trypan blue exclusion and DEVDase activity assays. Gene and protein expression changes were assessed by RT-PCR and western blot.

Results

ATO induced an antioxidant response characterised by Nrf2 nuclear translocation and enhanced transcription of downstream tar

SUBMITTER: Valenzuela M 

PROVIDER: S-EPMC4150280 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature