AB186 Inhibits Migration of Triple-Negative Breast Cancer Cells and Interacts with α-Tubulin.
Marine GeoffroyMarine LemesleAlexandra KleinclaussSabine MazerbourgLevy BatistaMuriel Barberi-HeyobThierry BastogneWilfrid BoireauAlain RouleauDorian DupommierMichel BoisbrunCorinne ComoyStéphane FlamentIsabelle Grillier-VuissozSandra KuntzPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- cell cycle arrest
- cell death
- induced apoptosis
- cell migration
- pi k akt
- breast cancer cells
- single cell
- cell therapy
- oxidative stress
- high throughput
- computed tomography
- cell proliferation
- high glucose
- diabetic rats
- young adults
- high resolution
- smoking cessation
- anti inflammatory
- drug induced
- endothelial cells
- quantum dots
- human health
- sensitive detection
- replacement therapy