Research Article
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Meme kanserinde Kv 1.3 ve Kv 10.1 voltaj bağımlı potasyum kanallarının inhibisyonunun oksidatif stres üzerindeki rolü

Year 2017, Volume: 44 Issue: 1, 43 - 50, 17.03.2017

Didem Turgut Coşan Çağrı Öner Ahu Soyocak Evrim Metcalfe Mustafa Djamgoz

https://doi.org/10.5798/dicletip.298591
Cited By: 1

Abstract

Amaç: Reaktif oksijen türevleri oksidatif stres, iyonize radyasyon maruziyeti, iskemi-reperfüzyon hasarı ve kanseri içeren fizyolojik ve patolojik durumlarda artmaktadır. Çalışmamızda meme kanser hücrelerinin farklılaşmasında ve çoğalmasında etkili olduğu düşünülen voltaj kapılı potasyum kanallarının inhibisyonunun etkilerini gözlemek amaçlandı.
Yöntemler: Farklı karakterlerdeki meme kanseri hücrelerine bu potasyum kanallarına özgü siRNA’ların transfeksiyon işlemi yapıldı. İnkübasyon sonrasında hücre lizatları hazırlanarak antioksidan ve oksidan seviyeleri belirlendi. Elde edilen verilerle oksidatif stres hesaplandı. Sürekli değişkenlerin normal dağılıma uygunluğu Kolmogorov-Smirnov testi kullanılarak yapıldı. Normal dağılım gösteren değişkenlerin gruplar arasındaki karşılaştırmaları tek yönlü varyans analizi ile değerlendirildi. Çoklu karşılaştırmalar ise Tukey HSD testi ile gerçekleştirildi.
Bulgular: Kanal inhibisyonu ile invaziv olmayan karakterdeki MCF-7 hücrelerinin oksidatif stres seviyesinde düşüş olduğu gözlendi. İnvaziv karakterdeki MDA-MB-231 hücrelerinde ise Kv 1.3 siRNA transfekte edilen grupta oksidatif stres seviyesinde düşüş belirlenirken, Kv 10.1 siRNA transfekte edilen grupta artış belirlendi.
Sonuç: Voltaj kapılı potasyum iyon kanallarının inhibisyonunun kanser hücrelerinde oksidatif stres oluşturabileceği belirlenmiştir. Ayrıca, çalışmamızdaki en önemli bulgu kanser hücrelerinde voltaj bağımlı potasyum kanallarının oksidatif stres üzerinde etki yapabileceği ve bunun hücrelerin metastatik karakteri ve iyon kanalı türü ile bağlantılı olmasıdır.

Keywords

Kv 1.3; Kv 10.1; meme kanseri; oksidatif stres

References

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  • 2. Yoshihara D, Fujiwara N, Suzuki K. Antioxidants: Benefits and risks for long-term health. Maturitas. 2010; 67:103-7.
  • 3. Cejas P, Casado E, Belda-Iniesta C, et al. Implications of oxidative stress and cell membrane lipid peroxidation in human cancer (Spain). Cancer Causes Control. 2004; 15:707-19.
  • 4. Laurent A, Nicco C, Chereau C, et al. Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res. 2005; 65:948-56.
  • 5. Skrzydlewska E, Kozuszko B, Sulkowska M, et al. Antioxidant potential in esophageal, stomach and colorectal cancers. Hepatogastroenterology. 2003; 50:126-31.
  • 6. Lehmann-Horn F, Jurkat-Rott K. Voltage-gated ion channels and hereditary disease. Physiol Rev. 1999; 79:1317-72.
  • 7. Zhang L, Zou W, Zhou SS, Chen DD. Potassium channels and proliferation and migration of breast cancer cells. Sheng Li Xue Bao. 2009; 61:15-20.
  • 8. Nerbonne JM, Kass RS. Molecular physiology of cardiac repolarization. Physiol Rev. 2005; 85:1205-53.
  • 9. Cahalan MD, Chandy KG. The functional network of ion channels in T lymphocytes. Immunol Rev. 2009; 231:59-87.
  • 10. Pardo LA, Stuhmer W. The roles of K(+) channels in cancer. Nat Rev Cancer. 2014;14:39-48.
  • 11. Brevet M, Fucks D, Chatelain D, et al. Deregulation of 2 potassium channels in pancreas adenocarcinomas: implication of KV1.3 gene promoter methylation. Pancreas. 2009; 38:649-54.
  • 12. Jang SH, Kang KS, Ryu PD, Lee SY. Kv1.3 voltage-gated K+ channel subunit as a potantial diagnostic marker and therapeutic target for breast cancer. BMB Rep. 2009; 42:535-9.
  • 13. Pardo LA, Contreras-Jurado C, Zientkowska M, et al. Role of voltage-gated potassium channels in cancer. J Membr Biol. 2005; 205:115-24.
  • 14. Downie BR, Sanchez A, Knotgen H, et al. Eag1 expression interferes with hypoxia homeostasis and induces angiogenesis in tumors. The Journal of biological chemistry. 2008; 283:36234-40.
  • 15. Yu SP. Regulation and critical role of potassium homeostasis in apoptosis. Prog Neurobiol. 2003; 70:363-86.
  • 16. Morton MJ, Chipperfield S, Abohamed A, et al. Na(+)-induced inward rectification in the two-pore domain K(+) channel, TASK-2. Am J Physiol Renal Physiol. 2005; 288:F162-9.
  • 17. Jang SH, Choi SY, Ryu PD, Lee SY. Anti-proliferative effect of Kv1.3 blockers in A549 human lung adenocarcinoma in vitro and in vivo. Eur J Pharmacol 2011; 651:26-32.
  • 18. Laniado ME, Fraser SP, Djamgoz MB. Voltage-gated K(+) channel activity in human prostate cancer cell lines of markedly different metastatic potential: distinguishing characteristics of PC-3 and LNCaP cells. The Prostate. 2001; 46:262-74.
  • 19. Ahidouch HO, Ahidouch A. K+ Channel Expression in Human Breast Cancer Cells: Involvement in Cell Cycle Regulation and Carcinogenesis. J Membrane Biol. 2008; 221:1-6.
  • 20. Feng JF, Lu L, Zeng P, et al. Serum total oxidant/antioxidant status and trace element levels in breast cancer patients. International journal of clinical oncology. 2012; 17:575-83.
  • 21. Pande D, Negi R, Khanna S, et al. Vascular endothelial growth factor levels in relation to oxidative damage and antioxidant status in patients with breast cancer. J Breast Cancer. 2011; 14:181-4.
  • 22. Abdul M, Santo A, Hoosein N. Activity of potassium channel-blockers in breast cancer. Anticancer Res. 2003;23: 3347-51.
  • 23. Leanza L, Venturini E, Kadow S, et al. Targeting a mitochondrial potassium channel to fight cancer. Cell Calcium. 2015; 58:131-8.
  • 24. Szabò I, Soddemann M, Leanza L, et al. Single-point muta-tions of a lysine residue change function of Bax and Bcl-xL expressed in Bax-and Bak-less mouse embryonic fibroblasts: novel insights into the molec-ular mechanisms of Bax-induced apoptosis. Cell Death Differ. 2011; 18:427-38.
  • 25. Leanza L, Henry B, Sassi N, et al. Inhibitors of mitochondrial Kv1.3 channels induce Bax/Bak-independent death of cancer cells. EMBO molecular medicine. 2012; 4:577-93.
  • 26. Leanza L, Trentin L, Becker KA, et al. Clofazimine, Psora-4 and PAP-1, inhibitors of the potassium channel Kv1.3, as a new and selective therapeutic strategy in chronic lymphocytic leukemia. Leukemia. 2013; 27:1782-5.
  • 27. Malinska D, Mirandola SR, Kunz WS. Mitochondrial potassium channels and reactive oxygen species. FEBS letters. 2010; 584:2043-8.
  • 28. Leanza L, Zoratti M, Gulbins E, Szabo I. Induction of Apoptosis in Macrophages via Kv1.3 and Kv1.5 Potassium Channels. Current Medicinal Chemistry. 2012; 19:5394-404.
  • 29. Dooley KE, Obuku EA, Durakovic N, et al. World Health Organization group 5 drugs for the treatment of drug-resistant tuberculosis: unclear efficacy or untapped potential? The Journal of infectious diseases. 2013; 207:1352-8.
  • 30. Wang Q, Hu W, Lei M, et al. MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress. PLoS One 2013; 8.
  • 31. Spitzner M, Martins JR, Soria RB, et al. Eag1 and Bestrophin 1 are up-regulated in fast-growing colonic cancer cells. The Journal of biological chemistry. 2008; 283:7421-8.
  • 32. Agarwal JR, Griesinger F, Stuhmer W, Pardo LA. The potassium channel Ether a go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia. Molecular cancer. 2010; 9:18.
  • 33. Ouadid-Ahidouch H, Le Bourhis X, Roudbaraki M, et al. Changes in the K+ current-density of MCF-7 cells during progression through the cell cycle: possible involvement of a h-ether.a-gogo K+ channel. Receptors Channels. 2001; 7:345-56.
  • 34. Hammadi M, Chopin V, Matifat F, et al. Human ether a-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry. Journal of cellular physiology. 2012; 227:3837-46.
  • 35. Garcia-Becerra R, Diaz L, Camacho J, et al. Calcitriol inhibits Ether-a go-go potassium channel expression and cell proliferation in human breast cancer cells. Experimental cell research. 2010; 316:433-42.

Year 2017, Volume: 44 Issue: 1, 43 - 50, 17.03.2017

Didem Turgut Coşan Çağrı Öner Ahu Soyocak Evrim Metcalfe Mustafa Djamgoz

https://doi.org/10.5798/dicletip.298591
Cited By: 1

Abstract

References

  • 1. Lavanya G, Sivajyothi R, Manjunath M, Parthasarathy PR. Fate of biomolecules during carbon tetrachloride induced oxidative stress and protective nature of Ammoniac baccifera Linn.: A natural antioxidant. International Journal of Green Pharmacy. 2009; 3:300-5.
  • 2. Yoshihara D, Fujiwara N, Suzuki K. Antioxidants: Benefits and risks for long-term health. Maturitas. 2010; 67:103-7.
  • 3. Cejas P, Casado E, Belda-Iniesta C, et al. Implications of oxidative stress and cell membrane lipid peroxidation in human cancer (Spain). Cancer Causes Control. 2004; 15:707-19.
  • 4. Laurent A, Nicco C, Chereau C, et al. Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res. 2005; 65:948-56.
  • 5. Skrzydlewska E, Kozuszko B, Sulkowska M, et al. Antioxidant potential in esophageal, stomach and colorectal cancers. Hepatogastroenterology. 2003; 50:126-31.
  • 6. Lehmann-Horn F, Jurkat-Rott K. Voltage-gated ion channels and hereditary disease. Physiol Rev. 1999; 79:1317-72.
  • 7. Zhang L, Zou W, Zhou SS, Chen DD. Potassium channels and proliferation and migration of breast cancer cells. Sheng Li Xue Bao. 2009; 61:15-20.
  • 8. Nerbonne JM, Kass RS. Molecular physiology of cardiac repolarization. Physiol Rev. 2005; 85:1205-53.
  • 9. Cahalan MD, Chandy KG. The functional network of ion channels in T lymphocytes. Immunol Rev. 2009; 231:59-87.
  • 10. Pardo LA, Stuhmer W. The roles of K(+) channels in cancer. Nat Rev Cancer. 2014;14:39-48.
  • 11. Brevet M, Fucks D, Chatelain D, et al. Deregulation of 2 potassium channels in pancreas adenocarcinomas: implication of KV1.3 gene promoter methylation. Pancreas. 2009; 38:649-54.
  • 12. Jang SH, Kang KS, Ryu PD, Lee SY. Kv1.3 voltage-gated K+ channel subunit as a potantial diagnostic marker and therapeutic target for breast cancer. BMB Rep. 2009; 42:535-9.
  • 13. Pardo LA, Contreras-Jurado C, Zientkowska M, et al. Role of voltage-gated potassium channels in cancer. J Membr Biol. 2005; 205:115-24.
  • 14. Downie BR, Sanchez A, Knotgen H, et al. Eag1 expression interferes with hypoxia homeostasis and induces angiogenesis in tumors. The Journal of biological chemistry. 2008; 283:36234-40.
  • 15. Yu SP. Regulation and critical role of potassium homeostasis in apoptosis. Prog Neurobiol. 2003; 70:363-86.
  • 16. Morton MJ, Chipperfield S, Abohamed A, et al. Na(+)-induced inward rectification in the two-pore domain K(+) channel, TASK-2. Am J Physiol Renal Physiol. 2005; 288:F162-9.
  • 17. Jang SH, Choi SY, Ryu PD, Lee SY. Anti-proliferative effect of Kv1.3 blockers in A549 human lung adenocarcinoma in vitro and in vivo. Eur J Pharmacol 2011; 651:26-32.
  • 18. Laniado ME, Fraser SP, Djamgoz MB. Voltage-gated K(+) channel activity in human prostate cancer cell lines of markedly different metastatic potential: distinguishing characteristics of PC-3 and LNCaP cells. The Prostate. 2001; 46:262-74.
  • 19. Ahidouch HO, Ahidouch A. K+ Channel Expression in Human Breast Cancer Cells: Involvement in Cell Cycle Regulation and Carcinogenesis. J Membrane Biol. 2008; 221:1-6.
  • 20. Feng JF, Lu L, Zeng P, et al. Serum total oxidant/antioxidant status and trace element levels in breast cancer patients. International journal of clinical oncology. 2012; 17:575-83.
  • 21. Pande D, Negi R, Khanna S, et al. Vascular endothelial growth factor levels in relation to oxidative damage and antioxidant status in patients with breast cancer. J Breast Cancer. 2011; 14:181-4.
  • 22. Abdul M, Santo A, Hoosein N. Activity of potassium channel-blockers in breast cancer. Anticancer Res. 2003;23: 3347-51.
  • 23. Leanza L, Venturini E, Kadow S, et al. Targeting a mitochondrial potassium channel to fight cancer. Cell Calcium. 2015; 58:131-8.
  • 24. Szabò I, Soddemann M, Leanza L, et al. Single-point muta-tions of a lysine residue change function of Bax and Bcl-xL expressed in Bax-and Bak-less mouse embryonic fibroblasts: novel insights into the molec-ular mechanisms of Bax-induced apoptosis. Cell Death Differ. 2011; 18:427-38.
  • 25. Leanza L, Henry B, Sassi N, et al. Inhibitors of mitochondrial Kv1.3 channels induce Bax/Bak-independent death of cancer cells. EMBO molecular medicine. 2012; 4:577-93.
  • 26. Leanza L, Trentin L, Becker KA, et al. Clofazimine, Psora-4 and PAP-1, inhibitors of the potassium channel Kv1.3, as a new and selective therapeutic strategy in chronic lymphocytic leukemia. Leukemia. 2013; 27:1782-5.
  • 27. Malinska D, Mirandola SR, Kunz WS. Mitochondrial potassium channels and reactive oxygen species. FEBS letters. 2010; 584:2043-8.
  • 28. Leanza L, Zoratti M, Gulbins E, Szabo I. Induction of Apoptosis in Macrophages via Kv1.3 and Kv1.5 Potassium Channels. Current Medicinal Chemistry. 2012; 19:5394-404.
  • 29. Dooley KE, Obuku EA, Durakovic N, et al. World Health Organization group 5 drugs for the treatment of drug-resistant tuberculosis: unclear efficacy or untapped potential? The Journal of infectious diseases. 2013; 207:1352-8.
  • 30. Wang Q, Hu W, Lei M, et al. MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress. PLoS One 2013; 8.
  • 31. Spitzner M, Martins JR, Soria RB, et al. Eag1 and Bestrophin 1 are up-regulated in fast-growing colonic cancer cells. The Journal of biological chemistry. 2008; 283:7421-8.
  • 32. Agarwal JR, Griesinger F, Stuhmer W, Pardo LA. The potassium channel Ether a go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia. Molecular cancer. 2010; 9:18.
  • 33. Ouadid-Ahidouch H, Le Bourhis X, Roudbaraki M, et al. Changes in the K+ current-density of MCF-7 cells during progression through the cell cycle: possible involvement of a h-ether.a-gogo K+ channel. Receptors Channels. 2001; 7:345-56.
  • 34. Hammadi M, Chopin V, Matifat F, et al. Human ether a-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry. Journal of cellular physiology. 2012; 227:3837-46.
  • 35. Garcia-Becerra R, Diaz L, Camacho J, et al. Calcitriol inhibits Ether-a go-go potassium channel expression and cell proliferation in human breast cancer cells. Experimental cell research. 2010; 316:433-42.
There are 35 citations in total.

Details

Subjects Health Care Administration
Journal Section Research Articles
Authors

Didem Turgut Coşan

Çağrı Öner This is me

Ahu Soyocak This is me

Evrim Metcalfe This is me

Mustafa Djamgoz This is me

Publication Date March 17, 2017
Submission Date March 17, 2017
Published in Issue Year 2017 Volume: 44 Issue: 1

Cite

APA Coşan, D. T., Öner, Ç., Soyocak, A., Metcalfe, E., et al. (2017). Meme kanserinde Kv 1.3 ve Kv 10.1 voltaj bağımlı potasyum kanallarının inhibisyonunun oksidatif stres üzerindeki rolü. Dicle Tıp Dergisi, 44(1), 43-50. https://doi.org/10.5798/dicletip.298591
AMA Coşan DT, Öner Ç, Soyocak A, Metcalfe E, Djamgoz M. Meme kanserinde Kv 1.3 ve Kv 10.1 voltaj bağımlı potasyum kanallarının inhibisyonunun oksidatif stres üzerindeki rolü. diclemedj. March 2017;44(1):43-50. doi:10.5798/dicletip.298591
Chicago Coşan, Didem Turgut, Çağrı Öner, Ahu Soyocak, Evrim Metcalfe, and Mustafa Djamgoz. “Meme Kanserinde Kv 1.3 Ve Kv 10.1 Voltaj bağımlı Potasyum kanallarının Inhibisyonunun Oksidatif Stres üzerindeki Rolü”. Dicle Tıp Dergisi 44, no. 1 (March 2017): 43-50. https://doi.org/10.5798/dicletip.298591.
EndNote Coşan DT, Öner Ç, Soyocak A, Metcalfe E, Djamgoz M (March 1, 2017) Meme kanserinde Kv 1.3 ve Kv 10.1 voltaj bağımlı potasyum kanallarının inhibisyonunun oksidatif stres üzerindeki rolü. Dicle Tıp Dergisi 44 1 43–50.
IEEE D. T. Coşan, Ç. Öner, A. Soyocak, E. Metcalfe, and M. Djamgoz, “Meme kanserinde Kv 1.3 ve Kv 10.1 voltaj bağımlı potasyum kanallarının inhibisyonunun oksidatif stres üzerindeki rolü”, diclemedj, vol. 44, no. 1, pp. 43–50, 2017, doi: 10.5798/dicletip.298591.
ISNAD Coşan, Didem Turgut et al. “Meme Kanserinde Kv 1.3 Ve Kv 10.1 Voltaj bağımlı Potasyum kanallarının Inhibisyonunun Oksidatif Stres üzerindeki Rolü”. Dicle Tıp Dergisi 44/1 (March 2017), 43-50. https://doi.org/10.5798/dicletip.298591.
JAMA Coşan DT, Öner Ç, Soyocak A, Metcalfe E, Djamgoz M. Meme kanserinde Kv 1.3 ve Kv 10.1 voltaj bağımlı potasyum kanallarının inhibisyonunun oksidatif stres üzerindeki rolü. diclemedj. 2017;44:43–50.
MLA Coşan, Didem Turgut et al. “Meme Kanserinde Kv 1.3 Ve Kv 10.1 Voltaj bağımlı Potasyum kanallarının Inhibisyonunun Oksidatif Stres üzerindeki Rolü”. Dicle Tıp Dergisi, vol. 44, no. 1, 2017, pp. 43-50, doi:10.5798/dicletip.298591.
Vancouver Coşan DT, Öner Ç, Soyocak A, Metcalfe E, Djamgoz M. Meme kanserinde Kv 1.3 ve Kv 10.1 voltaj bağımlı potasyum kanallarının inhibisyonunun oksidatif stres üzerindeki rolü. diclemedj. 2017;44(1):43-50.

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