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

Year 2018, Volume: 27 Issue: 1, 48 - 54, 01.03.2018

Seda Orenay Boyacıoglu

Abstract

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.

Keywords

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

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

Abstract

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

Keywords

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

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