Targeting Voltage-Gated Potassium Channels in Breast Cancer: Mechanistic Insights into 4-Aminopyridine-Induced Cell Death
International Journal of Molecular Sciences, cilt.26, sa.16, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 26 Sayı: 16
- Basım Tarihi: 2025
- Doi Numarası: 10.3390/ijms26167768
- Dergi Adı: International Journal of Molecular Sciences
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
- Anahtar Kelimeler: breast cancer cell line, intracellular Ca concentration, ion channel blockers, membrane potential, voltage-gated K channels
- Maltepe Üniversitesi Adresli: Evet
Özet
Cancer has recently been proposed as a type of channelopathy due to the aberrant expression of various ion channels. Voltage-gated potassium (K+) channels (VGKCs) are notably upregulated during tumor proliferation, while voltage-gated sodium (Na+) channels are predominantly associated with the invasive stage of cancer progression. Among these, the Kv10.1 channel has been found to be overexpressed in breast cancer, making it a promising therapeutic target. 4-Aminopyridine (4-AP), a non-selective voltage-gated potassium channel blocker, has emerged as a potential novel agent for breast cancer treatment. In this study, we aimed to elucidate the mechanism of action of 4-aminopyridine in breast cancer cells. To investigate the involvement of various cell death pathways, cycloheximide (CHX) (a paraptosis inhibitor), Z-VAD-FMK (a pan-caspase inhibitor), and 2-Aminoethoxydiphenyl borate (2-APB) (a phosphoinositide 3-kinase [PI3K] inhibitor) were employed. Experiments were conducted using the MCF-7 human breast cancer cell line and the L929 mouse fibroblast cell line as a healthy control. Assessments included cell viability assays, intracellular calcium (Ca2+) and K+ concentration measurements, and plasma membrane potential analysis. Our findings aim to contribute to the understanding of the therapeutic potential and cellular effects of VGKC blockers, particularly 4-aminopyridine, in breast cancer treatment strategies.