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.


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-gamma more than RAR-alpha.


CONCLUSIONS
The findings indicate that IIF transcriptionally activates RXR-gamma preferentially, induces apoptosis and has a more antiproliferative activity than ATRA and 9-cis RA on cell line HL-60.
Orlandi
M
M
Dipartimento di Biologia Evoluzionistica Sperimentale, Sezione di Microbiologia, Università di Bologna, Bologna, Italia. orlamari@alma.unibo.it
Mantovani
B
B
Ammar
K
K
Avitabile
E
E
Dal Monte
P
P
Bartolini
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D010616:Phenanthrenes / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology*
C476200:5-OH,11-O-hydrophenanthrene; D000970:Antineoplastic Agents; D010616:Phenanthrenes; D019253:Proto-Oncogene Proteins c-bcl-2; D018168:Receptors, Retinoic Acid; C105492:9,13-retinoic acid; D014212:Tretinoin