title: Δ2-Troglitazone promotes cytostatic rather than pro-apoptotic effects in breast cancer cells cultured in high serum conditions.
abstract: We have previously shown that Δ2-Troglitazone (Δ2-TGZ) displayed anticancer effects on breast cancer cell lines grown in low serum conditions (1% fetal calf serum (FCS)). The present study was performed in order to characterize the effects of Δ2-TGZ in high serum containing medium and to determine if starvation could influence the response of breast cancer cells to this compound, keeping in mind the potential interest for breast cancer therapy. We observed that in high serum conditions (10% FCS), a 48 h treatment with Δ2-TGZ induced a decrease in cell numbers in MDA-MB-231 and MCF-7 breast cancer cell lines. The IC50values were higher than in low serum conditions. Furthermore, in contrast to our previous results obtained in 1% FCS conditions, we observed that in 10% FCS-containing medium, MCF-7 cells were more sensitive to Δ2-TGZ than MDA-MB-231 cells. Δ2-TGZ also induced endoplasmic reticulum (ER) stress mainly in MDA-MB-231 cells. Besides, in high serum conditions, Δ2-TGZ induced a G0/G1cell cycle arrest, an inhibition of BrdU incorporation and a reduced level of cyclin D1. We observed a limited cleavage of PARP and a limited proportion of cells in sub-G1phase. Thus, in high serum conditions, Δ2-TGZ displayed cytostatic effects rather than apoptosis as previously reported in 1% FCS-containing medium. Our results are in accordance with studies suggesting that serum starvation could potentiate the action of diverse anti-cancer agents.
authors.affiliation: a Université de Lorraine, CRAN , UMR 7039, Vandœuvre-lès-Nancy , France.|b CNRS, CRAN , UMR 7039, Vandœuvre-lès-Nancy , France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Berthe
authors.affiliation: a Université de Lorraine, CRAN , UMR 7039, Vandœuvre-lès-Nancy , France.|b CNRS, CRAN , UMR 7039, Vandœuvre-lès-Nancy , France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Flament
authors.affiliation: a Université de Lorraine, CRAN , UMR 7039, Vandœuvre-lès-Nancy , France.|b CNRS, CRAN , UMR 7039, Vandœuvre-lès-Nancy , France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Grandemange
authors.affiliation: a Université de Lorraine, CRAN , UMR 7039, Vandœuvre-lès-Nancy , France.|b CNRS, CRAN , UMR 7039, Vandœuvre-lès-Nancy , France.
authors.forename: Marie
authors.initials: M
authors.lastname: Zaffino
authors.affiliation: c Université de Lorraine, SRSMC , UMR 7565, Vandœuvre-lès-Nancy , France.|d CNRS, SRSMC , UMR 7565, Vandœuvre-lès-Nancy , France.
authors.forename: Michel
authors.initials: M
authors.lastname: Boisbrun
authors.affiliation: a Université de Lorraine, CRAN , UMR 7039, Vandœuvre-lès-Nancy , France.|b CNRS, CRAN , UMR 7039, Vandœuvre-lès-Nancy , France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mazerbourg
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D002452:Cell Count; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D006801:Humans; D044967:Serum / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000378:metabolism; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
chemical_list: D002839:Chromans; D045162:Thiazolidinediones; D051742:Transcription Factor CHOP; D000077288:Troglitazone
keywords: Breast cancer; cell cycle; high serum conditions; low serum conditions; thiazolidinediones