Abstract
Novel compounds significantly interfering with the mitochondrial energy production may have therapeutic value in triple-negative breast cancer (TNBC). This criterion is clearly fulfilled by desethylamiodarone (DEA), which is a major metabolite of amiodarone, a widely used antiarrhythmic drug, since the DEA previously demonstrated anti-neoplastic, anti-metastasizing, and direct mitochondrial effects in B16F10 melanoma cells. Additionally, the more than fifty years of clinical experience with amiodarone should answer most of the safety concerns about DEA. Accordingly, in the present study, we investigated DEA’s potential in TNBC by using a TN and a hormone receptor positive (HR+) BC cell line. DEA reduced the viability, colony formation, and invasive growth of the 4T1 cell line and led to a higher extent of the MCF-7 cell line. It lowered mitochondrial transmembrane potential and induced mitochondrial fragmentation. On the other hand, DEA failed to significantly affect various parameters of the cellular energy metabolism as determined by a Seahorse live cell respirometer. Cyclooxygenase 2 (COX-2), which was upregulated by DEA in the TNBC cell line only, accounted for most of 4T1’s DEA resistance, which was counteracted by the selective COX-2 inhibitor celecoxib. All these data indicate that DEA may have potentiality in the therapy of TNBC.
Highlights
Breast cancer (BC) is the most frequent cancer type in women and the second primary cause of cancer-related death worldwide
By using the B16F10 melanoma cell line, we demonstrated that DEA affected mitochondrial processes in live cells [34] as it did previously in isolated liver and heart mitochondria [35]
The assay utilizes cell surface annexin V binding that measures the appearance of phosphatidylserine on the external surface of the plasma membrane, which is a marker of apoptosis
Summary
Breast cancer (BC) is the most frequent cancer type in women and the second primary cause of cancer-related death worldwide. TNBC patients typically present at a younger age a larger average tumor size, higher grade, and higher rates of lymph node positivity compared to patients with ER/PR-positive tumors [1]. Due to these features, TNBCs do not respond or became resistant to targeted therapies and, have poor prognosis [2]. Taxane- and anthracycline-based treatment represent the mainstream of TNBC chemotherapy, optimization of the protocols is yet to be accomplished [4]. Previous studies suggest that there is a correlation between inflammation and tumor formation [5], and intensive research is trying to uncover the complex interaction between breast cancer and the immune system [6,7]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.