Enhanced effects of PPARγ ligands and RXR selective retinoids in combination to inhibit migration and invasiveness in cancer cells

  • Authors:
    • A. Papi
    • P. Rocchi
    • A. M. Ferreri
    • F. Guerra
    • M. Orlandi
  • View Affiliations

  • Published online on: April 1, 2009     https://doi.org/10.3892/or_00000327
  • Pages: 1083-1089
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Abstract

Experimental data from in vitro and in vivo models indicate that peroxisome proliferator-activated receptor (PPAR) ligand activation regulates differentiation and induces cell growth arrest and apoptosis in a variety of cancer types. Thiazolidinediones such as ciglitazone (CGZ) constitute the most well-known synthetic ligands for PPARγ. We previously reported a remarkable antitumor effect of the retinoid 6-OH-11-O-hydroxyphenantrene (IIF), synthetic retinoid X receptors (RXRs) agonist, on many cancer cell lines. Since PPARs bind to DNA as heterodimers with RXRs, in this study we investigated if IIF potentiates the antitumoral properties of the PPARγ ligand CGZ in glioblastoma U87MG and melanoma G361 cells. Our results show that either IIF or CGZ inhibited cell growth and tissue invasion ability, but these properties were enhanced by using IIF and CGZ in combined treatment. Since matrix metalloproteinases (MMPs) play a major role in tumor cell invasion, we analyzed the effect of IIF and CGZ on MMP2 and MMP9 activity and expression. The addition of IIF to CGZ resulted in a decrease of MMP2 and MMP9 expression and activity, higher than when each agent was used alone. Furthermore, treatment with IIF and/or CGZ enhanced PPARγ expression but both agents in combined treatment caused the maximum efficiency. Finally, we demonstrated that IIF can potentiate PPARγ trascriptional activity induced by CGZ, by evaluation of peroxisome proliferator-responsive element transactivation. In conclusion, these findings suggest that the RXR selective retinoid IIF, in combination with the PPARγ ligand CGZ, may provide a therapeutic advantage in cancer treatment.

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April 2009
Volume 21 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Papi A, Rocchi P, Ferreri AM, Guerra F and Orlandi M: Enhanced effects of PPARγ ligands and RXR selective retinoids in combination to inhibit migration and invasiveness in cancer cells. Oncol Rep 21: 1083-1089, 2009
APA
Papi, A., Rocchi, P., Ferreri, A.M., Guerra, F., & Orlandi, M. (2009). Enhanced effects of PPARγ ligands and RXR selective retinoids in combination to inhibit migration and invasiveness in cancer cells. Oncology Reports, 21, 1083-1089. https://doi.org/10.3892/or_00000327
MLA
Papi, A., Rocchi, P., Ferreri, A. M., Guerra, F., Orlandi, M."Enhanced effects of PPARγ ligands and RXR selective retinoids in combination to inhibit migration and invasiveness in cancer cells". Oncology Reports 21.4 (2009): 1083-1089.
Chicago
Papi, A., Rocchi, P., Ferreri, A. M., Guerra, F., Orlandi, M."Enhanced effects of PPARγ ligands and RXR selective retinoids in combination to inhibit migration and invasiveness in cancer cells". Oncology Reports 21, no. 4 (2009): 1083-1089. https://doi.org/10.3892/or_00000327