Document Detail

Combined effects of interferon-alpha2a and 13-cis-retinoic acid on human melanoma cell growth and STAT protein expression.
MedLine Citation:
PMID:  9508374     Owner:  NLM     Status:  MEDLINE    
We assessed the antiproliferative effects of human recombinant interferon-alpha2a (IFNalpha2a) 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 IFNalpha2a 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 IFNalpha2a 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 IFNalpha2a markedly increased the nuclear expression of signal transducers and activators of transcription (STAT) proteins in both cell lines. By itself 10 microM 13cis-RA did not affect STAT protein expression or modify the extent of activation of such proteins by IFNalpha2a. Results from our study showed an enhancement of the antiproliferative activity of IFNalpha2a 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.
A Bearzatto; L Orlandi; R Silvestrini; F Belli; N Cascinelli; N Zaffaroni
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Melanoma research     Volume:  8     ISSN:  0960-8931     ISO Abbreviation:  Melanoma Res.     Publication Date:  1998 Feb 
Date Detail:
Created Date:  1998-05-14     Completed Date:  1998-05-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9109623     Medline TA:  Melanoma Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  31-8     Citation Subset:  IM    
Divisione di Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
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MeSH Terms
Cell Count / drug effects
Cell Cycle / drug effects
Cell Division / drug effects
DNA-Binding Proteins / metabolism*
Drug Combinations
Drug Synergism
Interferon Alfa-2a / pharmacology*
Isotretinoin / pharmacology*
Melanoma / drug therapy,  metabolism,  pathology*
STAT1 Transcription Factor
STAT2 Transcription Factor
Signal Transduction / drug effects
Trans-Activators / metabolism*
Tumor Cells, Cultured
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Drug Combinations; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/STAT2 Transcription Factor; 0/Trans-Activators; 4759-48-2/Isotretinoin; 76543-88-9/Interferon Alfa-2a

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