MCF-7 VE PC-3 HÜCRE HATLARINDA, HÜCRE CANLILIĞI VE DNA HASARI ÜZERİNE TRPV4 ANTAGONİSTİ RN 1734'ÜN ETKİLERİ

Amaç: Hücre içi kalsiyum (Ca 2+) sinyali; hücre proliferasyonu ve farklılaşması, gen transkripsiyonu, apoptozisgibi birçok hücresel süreçte rol oynar. Yapılan çalışmalarda Ca 2+ sinyalinin kanser ile ilişkili olduğu gösterilmişti. Transient receptor potentil vanilloid 4 (TRPV4) kanalları hücre zarında bulunan Ca 2+ geçirgennon-selekif katyon kanalıdır. TRPV4 kanalları vücutt birçok dokuda yaygın olarak eksprese edilmektedir.Hücre içi Ca 2+ miktarının düzenlenmesinde etkisi olan TRPV4 kanallarının kanser hücrelerinin proliferasyonu, apoptozis, migrasyonu ve tümor anjiogenezi ile ilgili önemli rolleri olduğu görülmüştür. Biz bu çalışmadaTRPV4 antagonist olan RN 1734’ün, insan prostat (PC-3) ve insan meme (MCF-7) kanseri hücre hatlarındahücre canlılığı ve DNA hasarı üzerine etkilerini araştıdık.Gereç ve Yöntemler: Çalışmamızda insan prostat (PC-3) ve insan meme (MCF-7) kanseri hücre hatları kullanıldı. RN 1734 1, 5, 25, 50 ve 100 μM’lik konsantrasyonlarda, 24 saatlik PC-3 ve MCF-7 hücre canlılığına olanetkisi 3-(4,5-dimetitizol-2-il)-2,5-difeniltetrazolyum bromid (MTT) yöntemiyle ölçüldü. RN 1734’ün DNAhasarına etkisi Comet yöntemine göre belirlendi.Bulgular: 24 saat süreyle RN 1734’ün özellikle 50 ve 100 μM’lik konsantrasyonlarıyla inkübe edilen PC-3 veMCF-7 hücrelerde canlılık düzeyi önemli ölçüde azaldı (p

Effect of TRPV4 Antagonist RN 1734 on DNA Damage and Cell Viability in MCF-7 and PC-3 Cell Lines

Aim: Intracellular calcium (Ca 2+) signal pathway has a role in cell proliferatin and diffrentitin, gene transcriptin and apoptosis. Studies have shown that Ca 2+ signal is related to cancer. Transient receptor potentil vanilloid 4 channels are Ca 2+ permeable non-selectie catin channels in the cell membrane. TRPV4 channels are commonly expressed in many tisues in the body. TRPV4 channels, which have an effct on the regulatin of intracellular Ca 2+ levels, have been shown to have important roles in the proliferatin, apoptosis, migratin and tumor angiogenesis of cancer cells. In this study, we investiated the effcts of RN 1734, TRPV4 antagonist, on cell viability and DNA damage in human prostate (PC-3) and human breast (MCF-7) cancer cell lines. Materials and Methods: Human prostate (PC-3) and human breast (MCF-7) cancer cell lines were used in our study. The effct of RN 1734 on 1, 5, 25, 50 and 100 μM concentratins on 24-hour PC-3 and MCF-7 cell viability was determined by 3- (4,5-dimethylthiazol-2-yl) -2,5- diphenyltetrazolium bromide (MTT) method. The effct of RN 1734 on DNA damage was determined according to Comet Assay method. Results: The viability of PC-3 and MCF-7 cells, which were incubated for 24 hours with RN 1734, especially at concentratins of 50 and 100 μM, was signifiantly reduced (p

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