The efficacy of 9-cis retinoic acid in experimental models of cancer

Breast Cancer Res Treat. 1996;38(1):85-96. doi: 10.1007/BF01803787.


9-cis retinoic acid (9-cis RA) is a retinoid receptor pan-agonist that binds with high affinity to both retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Using a variety of in vivo and in vitro cancer models, we present experimental data that 9-cis RA has activity as a potential chemotherapeutic agent. Treatment of the human promyelocytic leukemia cell line HL-60 with 9-cis RA decreases cell proliferation, increases cell differentiation, and increases apoptosis. Induction of apoptosis correlates with an increase in tissue transglutaminase (type II) activity. In vivo, 9-cis RA induces complete tumor regression of an early passage human lip squamous cell carcinoma xenograft. Finally, 9-cis RA inhibits the anchorage-independent growth of the human breast cancer cell lines MCF-7 and LY2 (an antiestrogen-resistant MCF-7 variant). Transient co-transfection assays indicate that 9-cis RA inhibits estrogen receptor transcription of an ERE-tk-LUC reporter through RAR or RXR receptors. These data suggest that retinoid receptors can antagonize estrogen-dependent transcription and provides one possible mechanism for the inhibition of cell growth by 9-cis RA in breast cancer cell lines. In summary, these findings present evidence that 9-cis RA has a wide range of activities in human cancer models.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy
  • Carcinoma, Squamous Cell / drug therapy
  • Cell Division / drug effects
  • HL-60 Cells / drug effects
  • Humans
  • Neoplasms / drug therapy*
  • Tretinoin / metabolism
  • Tretinoin / pharmacology
  • Tretinoin / therapeutic use*


  • Tretinoin