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Novel Therapeutic Approach: Ligands for PPARγ and Retinoid Receptors Induce Apoptosis in bcl-2-positive Human Breast Cancer Cells

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Abstract

Effective treatment of tumors is often associated with activation of the endogenous apoptosis pathways. We have studied eight breast cancer cell lines (MCF-7, BT20, BT474, MDA-MB-231, MDA-MB-436, SKBR3, T-47D, ZR-75-1) possessing a variety of genetic defects. The clonogenic growth of breast cancer cell lines was inhibited by a ligand for PPARγ (troglitazone, TGZ) combined with a ligand for either retinoid X receptor (RXR) (LG10069) (4/8 cell lines), RAR (ATRA) (5/8 cell lines) or RAR/RXR and RXR/RXR (9-cis-RA) (5/8 cell lines) independent of their expression of bcl-2, bag-1, ERα, and p53. The cell lines (MCF-7, T-47D, ZR-75-1), which expressed both BRCA1 and p27, were extremely sensitive to the inhibitory effect of the combination of TGZ and either ATRA or 9-cis-RA (ED90, 2-5 × 10−11 M). However, only MCF-7, MDA-MB-231, and ZR-75-1 cells, which expressed a high level of bcl-2 protein, underwent apoptosis when exposed to the combination of TGZ and either ATRA or 9-cis-RA. Importantly, this effect was independent of expression levels of p53, ERα, HER-2/neu, bag-1, and BRCA1. Therefore, the combination of ligands for PPARγ and retinoid receptors may have a therapeutic role for breast cancer.

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Authors and Affiliations

  1. Charite, Humboldt University, Berlin, Germany

    E. Elstner, C. Zang, J. Fritz, M. Fenner & K. Possinger

  2. Cedars-Sinai Medical Center, Los Angeles, CA, USA

    E.A. Williamson & H.P. Koeffler

  3. UCLA School of Medicine, Los Angeles, CA, USA

    D. Heber

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  1. E. Elstner
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Elstner, E., Williamson, E., Zang, C. et al. Novel Therapeutic Approach: Ligands for PPARγ and Retinoid Receptors Induce Apoptosis in bcl-2-positive Human Breast Cancer Cells. Breast Cancer Res Treat 74, 155–165 (2002). https://doi.org/10.1023/A:1016114026769

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