AB186 Inhibits Migration of Triple-Negative Breast Cancer Cells and Interacts with α-Tubulin

Breast cancer is one of the leading causes of cancer-related death among females worldwide. A major challenge is to develop innovative therapy in order to treat breast cancer subtypes resistant to current treatment. In the present study, we examined the effects of two Troglitazone derivatives Δ2-TGZ...

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Published in:International journal of molecular sciences 2022-06, Vol.23 (12), p.6859
Main Authors: Geoffroy, Marine, Lemesle, Marine, Kleinclauss, Alexandra, Mazerbourg, Sabine, Batista, Levy, Barberi-Heyob, Muriel, Bastogne, Thierry, Boireau, Wilfrid, Rouleau, Alain, Dupommier, Dorian, Boisbrun, Michel, Comoy, Corinne, Flament, Stéphane, Grillier-Vuissoz, Isabelle, Kuntz, Sandra
Format: Article
Language:English
Subjects:
Apoptosis
Breast cancer
Cancer
Cancer therapies
Cell adhesion & migration
Cellular Biology
Cytology
Cytoskeleton
Hypotheses
Life Sciences
Localization
Metastasis
Morphology
Pharmaceutical sciences
Pharmacology
Signal processing
Subcellular Processes
Surface plasmon resonance
Troglitazone
Tubulin
Wound healing
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Summary:Breast cancer is one of the leading causes of cancer-related death among females worldwide. A major challenge is to develop innovative therapy in order to treat breast cancer subtypes resistant to current treatment. In the present study, we examined the effects of two Troglitazone derivatives Δ2-TGZ and AB186. Previous studies showed that both compounds induce apoptosis, nevertheless AB186 was a more potent agent. The kinetic of cellular events was investigated by real-time cell analysis system (RTCA) in MCF-7 (hormone dependent) and MDA-MB-231 (triple negative) breast cancer (TNBC) cells, followed by cell morphology analysis by immuno-localization. Both compounds induced a rapid modification of both impedance-based signals and cellular morphology. This process was associated with an inhibition of cell migration measured by wound healing and transwell assays in TNBC MDA-MB-231 and Hs578T cells. In order to identify cytoplasmic targets of AB186, we performed surface plasmon resonance (SPR) and pull-down analyses. Subsequently, 6 cytoskeleton components were identified as potential targets. We further validated α-tubulin as one of the direct targets of AB186. In conclusion, our results suggested that AB186 could be promising to develop novel therapeutic strategies to treat aggressive forms of breast cancer such as TNBC.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23126859