Retinoids and malignant melanoma: a pathway of proliferation inhibition on SK MEL28 cell line.
BACKGROUND
It has been observed, in preclinical and clinical studies, that retinoids may interfere with the carcinogenic process in different ways such as the control of proliferation, differentiation and apoptosis.


METHODS
We evaluated the in vitro efficacy of some synthetic retinoids (RAR-alpha, beta and gamma; RXR-alpha agonists and RAR-alpha antagonist) and compared these to the panagonist all-trans retinoic acid in inhibiting growth of the human melanoma cell line, SK MEL 28. We estimated, in parallel, apoptosis as a function of the treatment and, by RT-PCR, we analysed the effects of retinoids on the transcriptional profile of relevant genes, such as retinoid receptors and regulatory proteins.


RESULTS
We observed a marked antiproliferative rate with the RAR-gamma selective agonist RO 44-4753 and the RAR-alpha selective antagonist RO 41-5253; on the contrary, the other synthetic retinoids exhibited a rather low efficacy. All the tested retinoids appeared to activate the RAR-beta gene and major expression was evidenced following RO 44-4753 and RO 41-5253 treatment.


CONCLUSIONS
Among the tested retinoids, RO 41-5253 exhibited marked effects on proliferation and RARs mRNA expression and its action appeared mainly related to a cell-cycle arrest rather than an apoptotic mechanism.
Emionite
Laura
L
Department of Oncology, Biology and Genetics, University of Genoa, National Institute for Cancer Research, Genoa, Italy.
Galmozzi
Fabia
F
Raffo
Patrizia
P
Vergani
Laura
L
Toma
Salvatore
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000037:antagonists & inhibitors; D012176:Retinoids / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D012176:Retinoids