Tetracaine downregulates matrix metalloproteinase activity and inhibits invasiveness of strongly metastatic MDA-MB-231 human breast cancer cells.

Autor: Keleş D; Izmir University of Economics, Vocational School of Health Services, Medical Laboratory Techniques, 35330, Balcova, Izmir, Turkey; Dokuz Eylül University, School of Medicine, Department of Medical Biochemistry, 35340, Inciralti, Izmir, Turkey., Sipahi M; Dokuz Eylül University, School of Medicine, Department of Medical Biochemistry, 35340, Inciralti, Izmir, Turkey., İnanç-Sürer Ş; Dokuz Eylül University, School of Medicine, Department of Medical Biochemistry, 35340, Inciralti, Izmir, Turkey., Djamgoz MB; Imperial College London, Department of Life Sciences, South Kensington Campus, SW7 2AZ, London, UK; Biotechnology Research Centre, Cyprus International University, Haspolat, Nicosia, TRNC, Mersin 10, Turkey., Oktay G; Dokuz Eylül University, School of Medicine, Department of Medical Biochemistry, 35340, Inciralti, Izmir, Turkey. Electronic address: gulgun.oktay@deu.edu.tr.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2023 Nov 01; Vol. 385, pp. 110730. Date of Electronic Publication: 2023 Oct 07.
DOI: 10.1016/j.cbi.2023.110730
Abstrakt: Tetracaine, a long-acting amino ester-type local anesthetic, prevents the initiation and propagation of action potentials by reversibly blocking voltage-gated sodium channels (VGSCs). These channels, which are highly expressed in several carcinomas (e.g. breast, prostate, colon and lung cancers) have been implicated in promoting metastatic behaviours. Recent evidence suggests that local anesthetics can suppress cancer progression. In this paper, we aimed to explore whether tetracaine would reduce the invasive characteristics of breast cancer cells. In a comparative approach, we used two cell lines of contracting metastatic potential: MDA-MB-231 (strongly metastatic) and MCF-7 (weakly metastatic). Tetracaine (50 μM and 75 μM) did not affect the proliferation of both MDA-MB-231 and MCF-7 cells. Importantly, tetracaine suppressed the migratory, invasive, and adhesive capacities of MDA-MB-231 cells; there was no effect on the motility of MCF-7 cells. Tetracaine treatment also significantly decreased the expression and activity levels of MMP-2 and MMP-9, whilst increasing TIMP-2 expression in MDA-MB-231 cells. On the other hand, VGSC α/Nav1.5 and VGSC-β1 mRNA and protein expression levels were not affected. We conclude that tetracaine has anti-invasive effects on breast cancer cells and may be exploited clinically, for example, in surgery and/or in combination therapies.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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