İmipraminin Mcf-7 Hücre Hattında Eag1 Potasyum Kanalları Üzerine Sitotoksik ve Elektrofizyolojik Etkileri
Abstract
Kanser hücrelerinde bazı iyon kanallarının aşırı eksprese edilmesi dikkat çekmektedir. Bu iyon kanallarından biri de Ether à-go-go 1 (KCNH1, Kv10.1) (Eag1 K+) kanalıdır. Bu çalışmada, MCF-7 hücre hattında (meme kanseri hücresi) trisiklik antidepresan olan imipraminin farklı konsantrasyonları kullanılarak, Eag1 K+ kanalları üzerine sitotoksik ve elektrofizyolojik etkileri incelenmiştir. Sitotoksik etkisi MTT analiz yöntemiyle, Elektrofizyolojik etkisi ise yama-kenetleme tekniği ile araştırılmıştır. MTT analiz yöntemiyle imipraminin MCF-7 hücreleri üzerinde kontrol grubuna göre 20μM ve üzeri konsantrasyonlarının yaklaşık %85 oranında baskılayıcı etkiye sahip olduğu belirlenmiştir. Yama-kenetleme deneylerinde MCF-7 hücrelerine 2μM, 5μM ve 20μM imipramin uygulanarak Eag1 K+ kanalları üzerine etkisi incelenmiştir. Düşük doz olan 2μM imipraminin kontrol grubuna göre Eag1 K+ kanal akımları yaklaşık %75 ve yüksek doz olan 20μM imipramin’in Eag1 K+ kanal akımlarını yaklaşık %82 gibi yüksek oranda inhibe ettiği gösterilmiştir.
Keywords
İmipramin Eag1 Potasyum Kanalı Meme Kanseri MCF-7 Hücre Hattı Elektrofizyoloji Sitotoksisite
Supporting Institution
Mersin Üniversitesi
Project Number
2021-1-TP2-4276
Thanks
BAP (Mersin Üniversitesi Bilimsel Araştırma Projeleri) Birimi tarafından 2021-1-TP2-4276 numaralı proje ile desteklenmiştir.
References
- Asher V., Sowter H., Shaw R., Bali A., Kahn R. Eag and HERG potassium channels as novel therapeutic targets in cancer. World Journal of Surgical Oncology 2010; 8(113): 1-9.
- Asher V., Warren A., Shaw R., Sowter H., Bali A., Khan, R. The role of Eag and ERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line. Cancer Cell International 2011; 11(6): 1-7.
- Blackiston D., McLaughlin K., Levin, M. Bioelectric controls of cell proliferation: ion channels, membrane voltage and the cell cycle. Cell Cycle 2009; 8(21): 3527-3536.
- Borowıec A., Hague F., Harır N., Gue´Nın S., Guerıneau F., Gouılleux F., Ouadıd-Ahıdouch H. IGF-1 activates hEAG KR channels through an akt-dependent signaling pathway in breast cancer cells: role in cell proliferation. Journal of Cellular Physiology 2007; 212(3): 690-701.
- Catterall, W., Chandy K., Gutman G. Introduction to the IUPHAR compendium of voltage-gated ion channels. Pharmacological Reviews 2005; 57(4): 385-385.
- García-Ferreiro R., Kerschensteiner D., Major F., Monje F., Stühmer W., Pardo L. Mechanism of block of hEag1 K+ channels by imipramine and astemizole. Journal of General Physiology 2004; 124(4): 301–317.
Cytotoxic and Electrophysiological Effects of Imipramine on Eag1 Potassium Channels in The Mcf-7 Cell Line
Abstract
It is noteworthy that some ion channels are overexpressed in cancer cells. One of these ion channels is the Ether à-go-go 1 (KCNH1, Kv10.1) (Eag1 K+) channel. In this study, cytotoxic and electrophysiological effects of different concentrations of tricyclic antidepressant, Imipramine, on Eag1 K+ channels were investigated in MCF-7 cell line (breast cancer cell). Its cytotoxic effect was investigated by MTT analysis method, and its electrophysiological effect was researched by patch-clamping technique. By MTT analysis, it was determined that 20 µM and higher concentrations of Imipramine on MCF-7 cells, had an approximately 85% suppressive effect, compared to the control group. On the other hand, in patch-clamping experiments, 2μM, 5μM and 20μM effects on Eag1 K+ channels were investigated. It has been shown that low-dose, 2μM Imipramine, inhibits Eag1 K+ channel currents by approximately 75% and its high-dose, 20μM, inhibits the channel currents by approximately 82%, compared to the control group.
Keywords
Imipramine Eag1 Potassium Channel Breast Cancer MCF-7 Cell Line Electrophysiology Cytotoxicity
Project Number
2021-1-TP2-4276
References
- Asher V., Sowter H., Shaw R., Bali A., Kahn R. Eag and HERG potassium channels as novel therapeutic targets in cancer. World Journal of Surgical Oncology 2010; 8(113): 1-9.
- Asher V., Warren A., Shaw R., Sowter H., Bali A., Khan, R. The role of Eag and ERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line. Cancer Cell International 2011; 11(6): 1-7.
- Blackiston D., McLaughlin K., Levin, M. Bioelectric controls of cell proliferation: ion channels, membrane voltage and the cell cycle. Cell Cycle 2009; 8(21): 3527-3536.
- Borowıec A., Hague F., Harır N., Gue´Nın S., Guerıneau F., Gouılleux F., Ouadıd-Ahıdouch H. IGF-1 activates hEAG KR channels through an akt-dependent signaling pathway in breast cancer cells: role in cell proliferation. Journal of Cellular Physiology 2007; 212(3): 690-701.
- Catterall, W., Chandy K., Gutman G. Introduction to the IUPHAR compendium of voltage-gated ion channels. Pharmacological Reviews 2005; 57(4): 385-385.
- García-Ferreiro R., Kerschensteiner D., Major F., Monje F., Stühmer W., Pardo L. Mechanism of block of hEag1 K+ channels by imipramine and astemizole. Journal of General Physiology 2004; 124(4): 301–317.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Structural Biology |
| Journal Section | RESEARCH ARTICLES |
| Authors | |
| Project Number | 2021-1-TP2-4276 |
| Publication Date | January 22, 2024 |
| Submission Date | May 24, 2023 |
| Acceptance Date | September 18, 2023 |
| Published in Issue | Year 2024 Volume: 7 Issue: 1 |
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