All-trans, 13-cis and 9-cis retinoic acids induce a fully reversible growth inhibition in HNSCC cell lines: Implications for in vivo retinoic acid use

Franca Giannini, Roberta Maestro, Tamara Vukosavljevic, Fabrizio Pomponi, Mauro Boiocchi

Research output: Contribution to journalArticlepeer-review

Abstract

Retinoids are a group of vitamin A analogues that have shown promise as chemopreventive and therapeutic agents in many types of malignancy and have been entered in clinical trials with some successful results. To better understand the mechanism that mediates retinoid action and the antiproliferative effects, we treated 7 human oral squamous-cell carcinoma (SCC) cell lines (FADU, HEp-2, CCL-17, SCC-9, SCC-15, SCC-25 and HN-212) with 10-6 M of all-trans retinoic acid (ATRA), 9-cis and 13-cis retinoic acid (RA) in continuous for different periods of time. We assessed the extent of growth inhibition, the stability of the anti-proliferative effect and the mRNA expression levels (by RT-PCR) of RA receptors (RARs), retinoid X receptors α (RXRα) and cytosolic RA-binding proteins (CRBP I and CRABP II) in treated cells compared with controls. The data obtained showed that all 3 RAs were able to inhibit the cellular growth of the tested cell lines, although to a different extent. The cis compounds were able to inhibit the proliferation of all cell lines, whereas ATRA was ineffective in inhibiting the proliferation of the CCL-17 cell line, which was naturally resistant to ATRA concentrations in the range between 10-5 and 10-6 M. All inhibitory effects were completely reversible since all cell lines restored their normal growth proliferation within few days after drug removal. RT-PCR analysis of the receptor and cell binding protein status of control and treated cells showed a good correlation between growth inhibition and induction of, or increase in, the expression levels of RARβ in RA-treated cells. No differences were observed in RARα and RXRα mRNA expression levels between control and treated cells. CRBP I, CRABP II and RARγ mRNA levels increased in some treated cell lines but not in all.

Original languageEnglish
Pages (from-to)194-200
Number of pages7
JournalInternational Journal of Cancer
Volume70
Issue number2
DOIs
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint

Dive into the research topics of 'All-trans, 13-cis and 9-cis retinoic acids induce a fully reversible growth inhibition in HNSCC cell lines: Implications for in vivo retinoic acid use'. Together they form a unique fingerprint.

Cite this