کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5504590 | 1400249 | 2017 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Rhodospirillum rubruml-asparaginase targets tumor growth by a dual mechanism involving telomerase inhibition
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کلمات کلیدی
RT-PCRMTVRRATGI3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromidehTERT - htertIU/ml - IU / میلی لیترMTT - MTTTelomerase - تلومراز Telomere length - طول telomereAntitumor activity - فعالیت ضد تومورTumor Growth Inhibition - مهار رشد تومورreverse transcription polymerase chain reaction - واکنش زنجیره ای پلیمراز رونویسی معکوس
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Rhodospirillum rubruml-asparaginase mutant RrA E149R, V150P, F151T (RrA) was previously identified to down-regulate telomerase activity along with catalyzing the hydrolysis of l-asparagine. The aim of this study was to define the effect of prolonged RrA exposure on telomerase activity, maintenance of telomeres and proliferation of cancer cells in vitro and in vivo. RrA could inhibit telomerase activity in SCOV-3, SkBr-3 and A549 human cancer cell lines due to its ability to down-regulate the expression of telomerase catalytic subunit hTERT. Telomerase activity in treated cells did not exceeded 29.63 ± 12.3% of control cells. Continuous RrA exposure of these cells resulted in shortening of telomeres followed by cell death in vitro. Using real time PCR we showed that length of telomeres in SCOV-3 cells has been gradually decreasing from 10105 ± 2530 b.p. to 1233 ± 636 b.p. after 35 days of cultivation. RrA treatment of xenograft models in vivo showed slight inhibition of tumor growth accompanied with 49.5-53.3% of decrease in hTERT expression in the all tumors. However down-regulation of hTERT expression, inhibition of telomerase activity and the loss of telomeres was significant in response to RrA administration in xenograft models. These results should facilitate further investigations of RrA as a potent therapeutic protein.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 492, Issue 2, 14 October 2017, Pages 282-288
Journal: Biochemical and Biophysical Research Communications - Volume 492, Issue 2, 14 October 2017, Pages 282-288
نویسندگان
Dmitry D. Zhdanov, Vadim S. Pokrovsky, Marina V. Pokrovskaya, Svetlana S. Alexandrova, Mikhail A. Eldarov, Dmitry V. Grishin, Marsel M. Basharov, Yulia A. Gladilina, Olga V. Podobed, Nikolai N. Sokolov,