Potassium channel inhibitors induce oxidative stress in breast cancer cells
Asian Biomedicine, cilt.11, sa.4, ss.323-330, 2017 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 11 Sayı: 4
- Basım Tarihi: 2017
- Doi Numarası: 10.1515/abm-2018-000
- Dergi Adı: Asian Biomedicine
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.323-330
- Anahtar Kelimeler: 4-aminopyridine, Astemizole, Breast cancer, Margatoxin, Oxidative stress, Tetraethylammonium chloride
- Maltepe Üniversitesi Adresli: Evet
Özet
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 (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. 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.