Pro-apoptotic effect of Δ2-TGZ in "claudin-1-low" triple-negative breast cancer cells: involvement of claudin-1

  • Breast Cancer Res Treat. 2017 Oct;165(3):517-527. doi: 10.1007/s10549-017-4378-2.
Marine Geoffroy  1  2 ,  Alexandra Kleinclauss  1  2 ,  Stéphanie Grandemange  1  2 ,  Sébastien Hupont  3 ,  Michel Boisbrun  4  5 ,  Stéphane Flament  1  2 ,  Isabelle Grillier-Vuissoz  6  7 ,  Sandra Kuntz  1  2
Affiliations
  • 1. Université de Lorraine, CRAN, UMR 7039, 54506, Vandœuvre-lès-Nancy, France.
  • 2. CNRS, CRAN, UMR 7039, 54506, Vandœuvre-lès-Nancy, France.
  • 3. CNRS, FR3209 Biologie Moléculaire Cellulaire et Thérapeutique (BMCT), Plateforme d'Imagerie Cellulaire et Tissulaire PTIBC-IBISA, Biopôle de l'Université de Lorraine, Campus Biologie-Santé, 54506, Vandœuvre-lès-Nancy, France.
  • 4. Université de Lorraine, SRSMC, UMR 7565, 54506, Vandœuvre-lès-Nancy, France.
  • 5. CNRS, SRSMC, UMR 7565, 54506, Vandœuvre-lès-Nancy, France.
  • 6. Université de Lorraine, CRAN, UMR 7039, 54506, Vandœuvre-lès-Nancy, France. [email protected].
  • 7. CNRS, CRAN, UMR 7039, 54506, Vandœuvre-lès-Nancy, France. [email protected].
PMID: 28681173 DOI: 10.1007/s10549-017-4378-2
Abstract

Purpose: 40% of triple-negative breast Cancer (TNBC) do not express claudin-1, a major constituent of tight junction. Patients with these "claudin-1-low" tumors present a higher relapse incidence. A major challenge in oncology is the development of innovative therapies for such poor prognosis tumors. In this context, we study the Anticancer effects of ∆2-TGZ, a compound derived from troglitazone (TGZ), on cell models of these tumors.

Methods and results: In MDA-MB-231 and Hs578T "claudin-1-low" TNBC cells, Δ2-TGZ treatment induced claudin-1 protein expression and triggered Apoptosis as measured by FACS analysis (annexin V/PI co-staining). Interestingly, in the non-tumorigenic human breast epithelial cell line MCF-10A, the basal level of claudin-1 was not modified following Δ2-TGZ treatment, which did not induce Apoptosis. Furthermore, claudin-1-transfected MDA-MB-231 and Hs578T cells displayed a significant increase of cleaved PARP-1 and Caspase 7, Caspase 3/7 activities, and TUNEL staining. RNA interference was performed in order to inhibit Δ2-TGZ-induced claudin-1 expression in both the cells. In absence of claudin-1, a decrease of cleaved PARP-1 and Caspase 7 and Caspase 3/7 activities were observed in MDA-MB-231 but not in Hs578T cells.

Conclusion: Claudin-1 overexpression and Δ2-TGZ treatment are associated to Apoptosis in MDA-MB-231 and Hs578T "claudin-1-low" TNBC. Moreover, in MDA-MB-231 cells, claudin-1 is involved in the pro-apoptotic effect of Δ2-TGZ. Our results suggest that claudin-1 re-expression could be an interesting therapeutic strategy for "claudin-1-low" TNBC.

Keywords
Apoptosis; Claudin-1; Triple-negative breast cancer; Troglitazone derivatives.
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