ROLE OF PTEN IN MODULATING PREVENTIVE EFFECT OF 3,4-DHPEA AGAINST OXIDATIVE STRES

Öz

Phosphate tensin homolog (PTEN) gen mutasyonuna sahip prostat kanseri (PCa) agresif hale gelebilir. Bu çalışmada, PCa hücre hatlarındaki PTEN mutasyonel durumunun, 3,4-dihydroxyphenyl ethanolün (3,4- DHPEA) kemopreventif etkisini değiştirebileceği ve böylece hücrelerin N,N,N′ ,N′ -Tetrakis(2- pyridylmethyl)ethylenediamine (TPEN) tarafından oluşturulan oksidatif stresi yönetme yeteneğini belirlediği hipotezi ileri sürülmüştür. Farklı PTEN statüsüne sahip DU-145 (PTEN +/−), 22Rv1 (PTEN +/+) ve PC3 (PTEN −/−) insan PCa hücre hatları 24 saat boyunca 100 µM'a kadar 3,4-DHPEA ve/veya 6,5 µM'a kadar TPEN ile muamele edildi. Muameleden sonra hücre canlılıkları Cell Titer-Glo Luminescent Assay ile ölçüldü ve varyans analizi testi ile analiz edildi. 50 μM kadar yüksek 3,4- DHPEA uygulaması 22Rv1 üzerinde en fazla sitotoksik etki gösterdi ve bunu DU-145 ve PC3 izledi. Benzer bir genel eğilim TPEN muamelesi ile de gözlemlendi. TPEN uygulamasnda IC50 değerleri 22Rv1 için 4.718 µM, DU145 için 4.963 μM ve PC3 için 5.245 μM idi. Hücrelerin IC50 dozunda TPEN ile birlikte 3,4-DHPEA ile muamelesi 3,4-DHPEA’nın yalnız uygulaması ile aynı şekilde sitotoksisite göstermiştir. 3,4-DHPEA'ya bağlı herhangi bir kemopreventif koruma etkisi gözlemlenmemiştir. Sonuçlar oksidatif stres oluşturan ajanların PTEN statüsüne bağlı oldukları hipotezi ile örtüşmektedir. Bu, wild tip PTEN içeren 22Rv1’in 3,4-DHPEA'ya karşı en büyük duyarlılığı göstermesi ile tutarlıdır.

Anahtar Kelimeler

• PTEN statüsü, TPEN, 3,4-DHPEA, oksidatif stres, prostat kanseri

Oksidatif Strese Karşı 3,4-Dhpea'nın Koruyucu Etkisinin Modülasyonunda Pten'in Rolü

Öz

Prostate cancer (PCa) with a Phosphate tensin homolog (PTEN) gene mutation can become aggressive. In this study, it was hypothesized that the PTEN mutational status in PCa cell lines might modify the chemopreventive effect of 3,4-dihydroxyphenyl ethanol (3,4-DHPEA), thus, determining the cells’ ability to manage oxidative stress created by N,N,N′ ,N′ -Tetrakis(2- pyridylmethyl)ethylenediamine (TPEN). The human PCa cell lines with varying PTEN status, DU-145 (PTEN +/−), 22Rv1 (PTEN +/+), and PC3 (PTEN −/−), were treated with up to 100 µM of 3,4-DHPEA and/or up to 6.5 µM of TPEN for 24 hours. The viability of cells after treatment was measured with Cell Titer-Glo Luminescent Assay and analyzed with the analysis of variance test. 3,4-DHPEA treatment as high as 50 µM had the greatest cytotoxic effect on 22Rv1 followed by DU-145 and PC3. Similar overall trend was also observed with TPEN treatment. When the cells were treated with TPEN at IC50 doses, 3,4-DHPEA co-treatment still showed cytotoxicity in the same order as 3,4-DHPEA treatment alone. No chemoprotective effect due to 3,4- DHPEA was observed. The data is still consistent with the hypothesis that oxidative stress inducing agents are dependent on the PTEN status. This is consistent with 22Rv1 with wild type PTEN showing the greatest susceptibility to 3,4-DHPEA

Anahtar Kelimeler

• PTEN status, TPEN, 3,4-DHPEA, oxidative stress, prostate cancer

Kaynakça

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