Associations of retinoids, tamoxifen and α-interferon 2a in human breast cancer: In vitro and in vivo studies

Salvatore Toma, Patrizia Raffo, Laura Isnardi, Lucia Riccardi, Elena De Francisci, Giuseppina Maselli, Giuseppe Dastoli, Raffaella Palumbo

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Abstract

We evaluated in vitro the potentiating and/or synergistic antitumor effects among retinoids (all-trans-retinoic acid, tRA, and 13-cis-retinoic acid, 13cRA), alpha-interferon 2a (α-IFN 2a) and tamoxifen (TAM) on both estrogen receptor positive (ER+) and negative (ER-) human breast cancer cell lines. In our experimental model, the three studied agents showed antiproliferative activity in ER+ cell lines MCF-7 and ZR-75.1, while α-IFN 2a was the most effective drug in the ER- cell line MDA-MB-231. Retinoids and TAM exerted a strong apoptotic effect in MCF-7 cells, while such an effect was obtained in MDA-MB-231 cells by α-IFN 2a. The tested combinations displayed different effects in the different evaluated cell lines: i) in MCF-7 cells tRA + TAM showed additive activity, both tRA + α-IFN 2a and TAM + α-IFN 2a association displayed a synergistic effect, and a further potentiation of the antiproliferative action was detected with the triple combination; ii) in ZR-75.1 cell line an additive activity was showed by tRA + TAM and TAM + α-IFN 2a, while tRA + α-IFN 2a produced synergistic action; iii) in MDA-MB-231 cell line only α-IFN 2a displayed a strong antiproliferative effect, and no significant potentiation was exerted by any drug association. The feasibility and activity of such combinations have been tested in two pilot clinical trials on patients with metastatic breast cancer: both the tested associations were tolerable, with good treatment compliance and low toxicity. The different antiproliferative and apoptotic effects observed in vitro on apparently similar breast cancer cell lines prompted us to a further investigation of the mutual biological modulations of these drug combinations, in view of a better selection of patients who might potentially benefit from these treatments.

Original languageEnglish
Pages (from-to)597-607
Number of pages11
JournalInternational Journal of Oncology
Volume10
Issue number3
Publication statusPublished - Mar 1997

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Keywords

  • breast cancer
  • interferon
  • retinoids
  • tamoxifen

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Toma, S., Raffo, P., Isnardi, L., Riccardi, L., De Francisci, E., Maselli, G., Dastoli, G., & Palumbo, R. (1997). Associations of retinoids, tamoxifen and α-interferon 2a in human breast cancer: In vitro and in vivo studies. International Journal of Oncology, 10(3), 597-607.