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01-10-2017 | Preclinical study

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

Authors: Marine Geoffroy, Alexandra Kleinclauss, Stéphanie Grandemange, Sébastien Hupont, Michel Boisbrun, Stéphane Flament, Isabelle Grillier-Vuissoz, Sandra Kuntz

Published in: Breast Cancer Research and Treatment | Issue 3/2017

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.

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Title: Pro-apoptotic effect of Δ2-TGZ in “claudin-1-low” triple-negative breast cancer cells: involvement of claudin-1
Authors: Marine Geoffroy
Alexandra Kleinclauss
Stéphanie Grandemange
Sébastien Hupont
Michel Boisbrun
Stéphane Flament
Isabelle Grillier-Vuissoz
Sandra Kuntz
Publication date: 01-10-2017
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-017-4378-2

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