# Comparison of Mitochondrial and Antineoplastic Effects of Amiodarone and Desethylamiodarone in MDA-MB-231 Cancer Line

## TL;DR

This study compares how amiodarone and its metabolite DEA affect mitochondria and cancer cell growth in a breast cancer cell line.

## Contribution

The study reveals that DEA is more effective than amiodarone in reducing mitochondrial function and cancer cell viability in TNBC cells.

## Key findings

- Both amiodarone and DEA reduced cancer cell viability and induced apoptosis in MDA-MB-231 cells.
- DEA was more effective than amiodarone in lowering mitochondrial ATP production and increasing mitochondrial fragmentation.
- DEA showed stronger antineoplastic effects, suggesting higher therapeutic potential for treating TNBC.

## Abstract

Previously, we have demonstrated that amiodarone (AM), a widely used antiarrhythmic drug, and its major metabolite desethylamiodarone (DEA) both affect several mitochondrial processes in isolated heart and liver mitochondria. Also, we have established DEA’s antitumor properties in various cancer cell lines and in a rodent metastasis model. In the present study, we compared AM’s and DEA’s mitochondrial and antineoplastic effects in a human triple-negative breast cancer (TNBC) cell line. Both compounds reduced viability in monolayer and sphere cultures and the invasive growth of the MDA-MB-231 TNBC line by inducing apoptosis. They lowered mitochondrial trans-membrane potential, increased Ca2+ influx, induced mitochondrial permeability transition, and promoted mitochondrial fragmentation. In accordance with their mitochondrial effects, both substances massively decreased overall, and even to a greater extent, mitochondrial ATP production decreased, as determined using a Seahorse live cell respirometer. In all these effects, DEA was more effective than AM, indicating that DEA may have higher potential in the therapy of TNBC than its parent compound.