Combined effects of interferon-α2a and 13-cis-retinoic acid on human melanoma cell growth and stat protein expression

A. Bearzatto, L. Orlandi, R. Silvestrini, F. Belli, N. Cascinelli, N. Zaffaroni

Research output: Contribution to journalArticle

Abstract

We assessed the antiproliferative effects of human recombinant interferon-α2a (IFNα2a) and 13-cis-retinoic acid (13cis-RA) on two human melanoma cell lines (JR8 and M14). Both cell lines showed a very modest sensitivity to IFNα2a and 13cis-RA as single agents. In JR8 cells, the combination of the two compounds consistently produced simple additive effects. In contrast, different effects of the combination were recorded in the M14 cell line depending on the treatment schedule. Specifically, an additive interaction was observed when IFNα2a and 13cis-RA were given in sequence, independently of the order of drug administration, whereas a supra-additive antiproliferative effect was seen when cells were simultaneously exposed to the two drugs. Exposure to 1000 IU/ml IFNα2a markedly increased the nuclear expression of signal transducers and activators of transcription (STAT) proteins in both cell lines. By itself 10 μM 13cis-RA did not affect STAT protein expression or modify the extent of activation of such proteins by IFNα2a. Results from our study showed an enhancement of the antiproliferative activity of IFNα2a and 13cis-RA when given in combination and suggest that such an enhancement is not mediated by a concomitant effect of 13cis-RA on STAT protein activation.

Original languageEnglish
Pages (from-to)31-38
Number of pages8
JournalMelanoma Research
Volume8
Issue number1
DOIs
Publication statusPublished - 1998

Keywords

  • Cell growth
  • Interferon
  • Melanoma cells
  • Retinoic acid
  • STAT proteins

ASJC Scopus subject areas

  • Cancer Research
  • Dermatology

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