Different effects of the treatment with AGN 193836 and 9-cis-retinoic acid in breast cancer cells.
Retinoid effects have been well studied in different cellular models, and their in vitro action on breast cancer is well known. Much less is known about the function of the different retinoid receptors in mediating retinoid activity in this and other cellular models. In order to better understand these biological mechanisms, several synthetic compounds have been produced, that have specific binding affinity for selected nuclear receptors, and their effect has been evaluated and confronted with that of classic compounds able to bind to different receptors. The aim of this study was the evaluation of the biological activities in breast cancer cell lines of one of these new compounds, AGN 193836, with a very selective binding affinity (selective agonist retinoid) for one single retinoic acid receptor (RAR alpha), in respect to a classic retinoid able to bind to a broad spectrum of retinoic acid receptors (pan-agonist retinoid), 9cRA. Our results clearly indicate that the selective retinoid retains most of the biological activities of the pan-agonist compound, but its effect is probably aggravated by fewer side-effects in vivo: This evidences indicate that selective-agonist retinoids are an interesting research field for the future, not only because of their speculative interest, but also in view of future clinical applications.
Isnardi
L
L
Pre-clinical Oncology Laboratory, Advanced Biotechnology Center (ABC), Genoa, Italy.
Raffo
P
P
Emionite
L
L
Chardraratna
R A
RA
Toma
S
S
D000077556:Alitretinoin; D062365:Aminobenzoates / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C100911:AGN 193836; D062365:Aminobenzoates; D018168:Receptors, Retinoic Acid; D013764:Tetrahydronaphthalenes; D000077556:Alitretinoin; D014212:Tretinoin