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.

MATERIALS AND 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.

CONCLUSION

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.