Potassium channel inhibitors induce oxidative stress in breast cancer cells
Article Category: Original article
Published Online: Mar 21, 2018
Page range: 323 - 330
DOI: https://doi.org/10.1515/abm-2018-0004
Keywords
© 2017 Çağri Öner, Ertuğrul Çolak, Didem Turgut Coşan
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.
Background
Antioxidant levels increase to protect cell homeostasis when oxidant generation is increased by drug or inhibitor treatment. If the oxidant–antioxidant equilibrium is disrupted, oxidative stress will occur.
Objectives
To determine the effects of various potassium channel inhibitors in the disruption of oxidant–antioxidant equilibrium in breast cancer cell lines with various phenotypes.
Methods
MCF-7 or MDA-MB-231 breast cancer cells were treated with tetraethylammonium chloride (5 mM; TEA), 4-aminopyridine (5 mM; 4-AP), margatoxin (25 nM; MgTX), or astemizole (200 nM; AST). After treatment, total antioxidant, oxidant, and oxidative stress levels were determined.
Results
Incubation with TEA, 4-AP, MgTX, and AST increased oxidative stress in both MCF-7 and MDA-MB-231 cells (
Conclusions
Potassium channel inhibitors used in our study disrupted the antioxidant–oxidant equilibrium and increased oxidative stress in the cancer cell lines. Although all of the channel inhibitors increased oxidative stress in cells, TEA and AST were the most effective inhibitors in MCF-7 cells. 4-AP was the most effective inhibitor in MDA-MB-231 cells. Voltage-gated potassium channels are attractive targets for anticancer therapy, and their inhibitors may enhance the effects of anticancer drugs.