<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_abm-2018-0004_s_005_w2aab3b7b3b1b6b1aab1c17b1Aa"><h3>Background</h3><p>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.</p></sec><sec id="j_abm-2018-0004_s_006_w2aab3b7b3b1b6b1aab1c17b2Aa"><h3>Objectives</h3><p>To determine the effects of various potassium channel inhibitors in the disruption of oxidant–antioxidant equilibrium in breast cancer cell lines with various phenotypes.</p></sec><sec id="j_abm-2018-0004_s_007_w2aab3b7b3b1b6b1aab1c17b3Aa"><h3>Methods</h3><p>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.</p></sec><sec id="j_abm-2018-0004_s_008_w2aab3b7b3b1b6b1aab1c17b4Aa"><h3>Results</h3><p>Incubation with TEA, 4-AP, MgTX, and AST increased oxidative stress in both MCF-7 and MDA-MB-231 cells (<italic>P</italic> &lt; 0.001). Specific inhibitors of calcium-activated potassium channels and <italic>ether á go-go</italic> 1-related potassium channels produce greater oxidative stress than other inhibitors in MCF-7 breast cancer cells, whereas in MDA-MB-231 cells, the nonselective channel inhibitor 4-AP produces the greatest oxidative stress.</p></sec><sec id="j_abm-2018-0004_s_009_w2aab3b7b3b1b6b1aab1c17b5Aa"><h3>Conclusions</h3><p>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.</p></sec></abstract>

BackgroundAntioxidant 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.ObjectivesTo determine the effects of various potassium channel inhibitors in the disruption of oxidant–antioxidant equilibrium in breast cancer cell lines with various phenotypes.MethodsMCF-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.ResultsIncubation with TEA, 4-AP, MgTX, and AST increased oxidative stress in both MCF-7 and MDA-MB-231 cells (P < 0.001). Specific inhibitors of calcium-activated potassium channels and ether á go-go 1-related potassium channels produce greater oxidative stress than other inhibitors in MCF-7 breast cancer cells, whereas in MDA-MB-231 cells, the nonselective channel inhibitor 4-AP produces the greatest oxidative stress.ConclusionsPotassium 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.

Potassium channel inhibitors induce oxidative stress in breast cancer cells

Department of Medical Biology, Medical Faculty

Department of Biostatics and Bioinformatics, Medical Faculty

Asian Biomedicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

{"article-title":"Potassium channel inhibitors induce oxidative stress in breast cancer cells"}

BackgroundAntioxidant levels increase to protect cell homeostasis when oxidant generation is increased by drug or inhibitor treatment. If the...

Potassium channel inhibitors induce oxidative stress in breast cancer cells

Article Category: Original article

Online veröffentlicht: 21. März 2018

Seitenbereich: 323 - 330

DOI: https://doi.org/10.1515/abm-2018-0004

Schlüsselwörter
4-aminopyridine, astemizole, breast cancer, margatoxin, oxidative stress, tetraethylammonium chloride

© 2017 Çağri Öner, Ertuğrul Çolak, Didem Turgut Coşan

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Figure 1

Figure 2

Potassium channel inhibitors induce oxidative stress in breast cancer cells

Article Category: Original article

Online veröffentlicht: 21. März 2018

Seitenbereich: 323 - 330

DOI: https://doi.org/10.1515/abm-2018-0004

Schlüsselwörter4-aminopyridine, astemizole, breast cancer, margatoxin, oxidative stress, tetraethylammonium chloride

© 2017 Çağri Öner, Ertuğrul Çolak, Didem Turgut Coşan

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Figure 1

Figure 2

Schlüsselwörter
4-aminopyridine, astemizole, breast cancer, margatoxin, oxidative stress, tetraethylammonium chloride