Potentiation of arsenic trioxide induced apoptosis by retinoic acid in retinoic acid sensitive and resistant HL-60 myeloid leukemia cells

Objective To study the effect of arsenic trioxide (As 2O 3) on non APL acute myeloid leukemia (AML) cells and the interreactive effect between retinoic acid (RA) and As 2O 3 Methods RA sensitive (S) and RA resistant (R) HL 60 non APL AML cells were used as an in vitro model Cell number and trypan blue were used to observe cell growth and survival Apoptosis was determined by morphological changes, using a DNA laddering assay, terminal deoxynucleotidyl transferase (TdT) fragment end labeling assay and a flow cytometry assay Results As 2O 3 induced apoptosis in both HL 60S and HL 60R cells, As 2O 3 induced apoptosis was both time and concentration dependent in a therapeutically achievable As 2O 3 range (0 25-4.0?μmol/L) Both all trans retinoic acid (ATRA) and 9 cis retinoic acid (9cRA) potentiated As 2O 3 induced apoptosis, as measured by quantitative TdT fragment end labeling and flow cytometry assays in both HL 60S and HL 60R cells ( P <0 05, for all RA+As 2O 3 combinations vs As 2O 3 alone in both sublines) Conclusions As 2O 3 may inhibit the growth of non APL AML cells by promoting programmed cell death RA can potentiate As 2O 3 induced apoptosis even in RA resistant HL 60 cells in which the classical ATRA response pathway is repressed owing to a homozygous inactivating mutation in the retinoic acid receptor α As 2O 3 can have clinical activity in non APL cases of AML and the enhanced activity might result from the combined As 2O 3 RA therapy

Retinoic acid signaling in fatty liver disease

Retinoic acid(RA)is a metabolite of vitamin A and is essential for development and growth as well as cellular metabolism.Through genomic and nongenomic actions,RA regulates a variety of physiological functions.Dysregulation of RA signaling is associated with many diseases.Targeting RA signaling has been proven valuable to human health.All-trans-RA(AtRA)and anthracycline-based chemotherapy are the standard treatment of acute promyelocytic leukemia(APL).Both human and animal studies have shown a significant relationship between RA signaling and the development and progression of nonalcoholic fatty liver disease(NAFLD).In this review article,we will first summarize vitamin A metabolism and then focus on the role of RA signaling in NAFLD.AtRA inhibits the development and progression of NAFLD by regulating lipid metabolism,inflammation,thermogenesis,etc.