Investigation of the effects of blocking potassium channelswith 4-aminopyridine on paclitaxel activity in breastcancer cell lines
Yükleniyor...
Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Background: Paclitaxel (PTX) has been used as a chemotherapeutic agent for several malignancies, including breast cancer, and efforts to increase the efficiency of PTX are continuous. Previous studies have shown that the voltage-gated K+ channels are over-expressed in breast cancer cell lines; therefore, blocking this type of K+ channel reduces cell proliferation and viability. Aims: In this study, FDA-approved 4-aminopyridine (4-AP), a voltage-gated potassium channel blocker, was used in combina tion with PTX to improve the anticancer activity of PTX in MCF-7 and MDA-MB-231 cell lines. Methods and Results: Viability was determined with trypan blue, a clonogenic assay was performed, and the cell cycle was determined with a flow cytometer and immunochemistry. To gain an insight into the mechanism, intracellular K+ concentration, intracellular Ca2+ (calcium) concentration, and transmembrane potential measurements were made with corresponding fluo rescent dyes. The apoptotic cell number was determined using Annexin /PI method by flow cytometer. Viability decreased with combination therapy and the clonogenic assay proved decreased colony formation. The apoptotic cell number was increased after treatment with the combination in both cell lines. Cell cycle measurements showed G1 arrest for both MCF-7 and MDA-MB-231 cell lines upon 4-AP treatment. PTX caused G1 arrest in MCF-7 cells and S phase arrest in MDA-MB-231 cells. Combination treatment caused S phase arrest in MCF-7 cells and S phase and G2/M phase arrest in MDA-MB-231 cells. Intracellular K+ con centration was increased after all treatments in both cell lines. Ca2+ concentration was increased significantly after combination treatment. Depolarization in the transmembrane potential was observed after all treatments in both cell lines. Conclusion: Biophysical parameters like the transmembrane potential and ion fluxes have been defined in cancer progression which can provide new aspects for cancer treatments. This study shows that the combination of 4-AP with PTX is a promising alternative the mechanism of which needs further investigation considering the results obtained for Ca2+, K+, and membrane potential.
Açıklama
Anahtar Kelimeler
Apoptosis, Breast Cancer, Cell Cycle, Drug Mechanism, Drug Repurposing, Transmembrane Potentia
Kaynak
Cancer Reports
WoS Q Değeri
Scopus Q Değeri
Cilt
7
Sayı
12
Künye
Cüce Aydoğmuş, E. M. ve İnhan Garip, G. A. (2024). Investigation of the effects of blocking potassium channelswith 4-aminopyridine on paclitaxel activity in breastcancer cell lines, Cancer Reports, Wiley, 7(12), s.1-10.
