The Effects And Possible Mechanism Of JWA And Bcl-2 Gene In As₂O₃ Combined With Vitamin C And/or GM-CSF-induced Cell Differentiation And Apoptosis In HL-60 And NB4 Cells

JWA (AF070523) is a novel all-trans retinoic acid (ATRA) responsible gene and was initially isolated from ATRA-treated primary human tracheal bronchial epithelial cells by Zhou et al. The full length of cDNA sequence of the gene contains 2114 nucleotides and a 567 base pairs (include stop coden TAA) of open reading frame (ORF) which encoding 188 amino acids. The molecular weight of JWA protein is 21.5 kDa. Within the identified 3000 base pairs of promoter sequence of the gene, we found several cis-action elements, such as phorbol ester response element (TRE), stress response element (SRE), and the retinoic acid response element (RARE) semi-site and so on. Our previous investigations have demonstrated that JWA was regulated by several chemicals (i.e. arsenic trioxide, ATRA, 4HPR, hemin) and environmental stressors (i.e. heat shock, oxidative stress), and may function associate with cell differentiation and apoptosis.Arsenic trioxide (As₂O₃ or ATO) has been identified as a potent anti-leukemic agent in patients with refractory and relapse acute promyelocytic leukemia (APL or M3) more than ten years. Recent preliminary reports suggest that the pro-apoptotic effect of ATO is not specific for APL but also observed in non-M3 acute myeloid leukemia (AML) cells, although these may display an up to 10-fold lower sensitivity to ATO than APL cells. Ascorbic acid (AA) has been found to be a promising agent in enhancing the effect of ATO in cells...