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

• Published in: Chemico-biological interactions 2023-11, Vol.385, p.110730-110730, Article 110730
• Main Authors: Keleş, Didem, Sipahi, Murat, İnanç-Sürer, Şeniz, Djamgoz, Mustafa BA, Oktay, Gülgün
• Format: Article
• Language: English
• Subjects: Breast cancer; Invasion; Matrix metalloproteinases; Tetracaine; Voltage-gated sodium channels
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2023.110730

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. •Tetracaine did not affect cell proliferation in MDA-MB-231 and MCF-7 cells.•No significant effect was observed in MCF-7 motility.•Tetracaine suppressed the metastatic cell behaviours of MDA-MB-231 cells.•MMP-2 and MMP-9 activities were decreased in tetracaine treated-MDA-MB-231 cells.•Nav1.5 and β1 expression levels were not altered with the tetracaine treatment.