Novel insights into the combined effect of triorganotin compounds and all-trans retinoic acid on expression of selected proteins associated with tumor progression in breast cancer cell line MDA-MB-231: Proteomic approach

Abstract

Trialkyltins and triaryltins function as nuclear retinoid X receptors (RXR) agonists due to their affinity to the ligand-binding domain of RXR subtypes and function as transcriptional activators. We present the data on combined effects of all-trans retinoic acid (ATRA), retinoic acid receptor (RAR) ligand and tributyltin chloride or triphenyltin chloride (RXR ligands) on protein pattern in MDA-MB-231 cells. Proteomic strategies based on bottom-up method were applied in this study. The total cell proteins were extracted, separated on 2D SDS-PAGE and their characterization was achieved by MALDI-TOF/TOF MS/MS. By employing PDQuest™ software, we identified more than 30 proteins differently affected by the above compounds. For further studies, we selected specific proteins associated either with metabolic pathway (glyceraldehyde-3-phosphate dehydrogenase) or to cellular processes as apoptosis, regulation of gene transcription or epithelial-mesenchymal transition (annexin 5, nucleoside diphosphate kinase B and vimentin). We have found that treatment of MDA-MB-231 cells with triorganotins reduced the expression of studied proteins. Moreover, the treatment of MDA-MB-231 cells with triorganotin compounds together with ATRA resulted in an additional reduction of annexin 5, vimentin and nucleoside diphosphate kinase B. These results demonstrate that RXR/RAR heterodimer may act under this experimental design as permissive heterodimer allowing activation of RXR by triorganotins.

CD44 and vimentin, markers involved with epithelial-mesenchymal transition: A proteomic analysis of sequential proteins extraction of triple-negative breast cancer cells after treatment with all-trans retinoic acid

“…ATRA, 9-cis retinoic acid, and a mixture of these two retinoic receptor ligands were tested by Flodrova et al (2017). The treatment of MDA-MB-231 cells with triorganotin compounds together with ATRA resulted in an additional reduction of annexin 5, nucleoside diphosphate kinase B and VIME (Strouhalova et al 2019(Strouhalova et al , 2020. In this work, the hypothesis of these studies which stated that ATRA led to a significant reduction in VIME as well as CD44 protein level was confirmed.…”

Use of Lectin-based Affinity Techniques in Breast Cancer Glycoproteomics: A Review

“…A major challenge of proteomics is to identify biomarkers for the screening of the initial stages of cancer and the prediction of therapeutic response. ,, Proteomics can also help us to look for new potential therapeutics and monitor their impact on cells. As an example, the influence of natural or synthetic retinoid treatment on breast cancer cells − and the study dealing with the treatment of breast cancer cells with an extract from a tropical plant, Lippia origanoides , can be cited.…”

Triorganotin complexes in cancer chemotherapy: Mechanistic insights and future perspectives

“…A study describing the combined effect of 1 or 2 with all‐ trans retinoic acid suggested that RXR/RAR may act as a permissive heterodimer, thus enabling triorganotin complexes to activate RXR together with all‐ trans retinoic acid. [ 110 ]…”

“…A study describing the combined effect of 1 or 2 with all-trans retinoic acid suggested that RXR/RAR may act as a permissive heterodimer, thus enabling triorganotin complexes to activate RXR together with all-trans retinoic acid. [110] Peroxisome proliferator-activated receptors (PPARs), namely, PPARα, PPARβ/δ, and PPARγ, constitute another family of nuclear hormone receptors. PPARs form heterodimers with RXR and activate several target genes that are associated with glucose and lipid metabolism, cellular growth, and differentiation.…”