Retinoids and cancer: Antitumoral effects of ATRA, 9-cis RA and the new retinoid IIF on the HL-60 leukemic cell line

Objective: To compare the antitumoral effects of all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) with those of 5-OH,11-O-hydrophenanthrene (IIF), a new derivative of retinoic acid. Materials and Methods: The effect of retinoids was tested on cell line HL-60. Cell differentiation and apoptosis were evaluated by morphological and biochemical analysis as bcl-2 protein and by DNA fragmentation assay. The ability to activate retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) and to modulate gene expression was determined by transactivation assay. Results: With cell line HL-60, the antiproliferative effect of IIF was stronger than that of ATRA and 9-cis RA. Following retinoid treatment, cells appeared to differentiate and apoptotic cells were observed. The appearance of DNA laddering and a decrease in the amount of bcl-2 protein confirmed apoptosis. IIF transcriptionally activated RXR-γ more than RAR-α. Conclusion: The findings indicate that IIF transcriptionally activates RXR-γ preferentially, induces apoptosis and has a more antiproliferative activity than ATRA and 9-cis RA on cell line HL-60. Copyright © 2003 S. Karger AG, Basel.