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

Abstract

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.

Synthesis of New Chromene Derivatives Targeting Triple-Negative Breast Cancer Cells

“…In addition, AB 186 has been shown to promote microtubule stabilization via direct binding to β-tubulin. AB 186 was also shown to affect an unorganized actin network in MDA-MB-231 cells [62]. Troglitazone itself was also shown to inhibit the migration of highly metastatic PK-1 (pancreatic) and ES-2 (ovarian) cancer cells via inhibition of actin polymerization, lamellipodia formation, and inducing a decrease in the number of actin stress fibers [63,64].…”

“…However, very few studies have investigated the effect of microtubule-targeting drugs on the integrity of the actin cytoskeleton in cancer cells. For example, AB 186, a troglitazone derivative and microtubule-stabilizing compound, inhibits the migration of the two highly metastatic TNBC cell lines, MDA-MB-231 and Hs578T [62]. In addition, AB 186 has been shown to promote microtubule stabilization via direct binding to β-tubulin.…”

Unexplored Vinylic-Substituted 5-Benzylidenethiazolidine-2,4-diones: Synthesis and DFT/NMR Stereochemical Assignment

“…5-Benzylidenethiazolidine-2,4-dione (BTZD) 1 is a privileged scaffold present in a wide range of bioactive molecules including antidiabetics, antivirals, anti-inflammatories, or antiproliferative compounds (Figure ). − …”

Editorial for the Special Issue “New Drugs for Breast Cancer Treatment”

“…In particular, the readers of this Special Issue will learn about the anti-tumor activity of neosynthesized, natural, and already-available drugs that could be used as new anti-BC drugs. Indeed, the contributing authors have reported the antiproliferative activity of berberine and troglitazone derivatives, resveratrol analogs, atoquavone, clotrimazole, fenticonazole, compounds specifically targeting mitochondrial activity, and valproic acid, as well as NAMPT and carbonic anhydrase IX inhibitors [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ].…”