کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8323482 | 1539891 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Wortmannin potentiates the combined effect of etoposide and cisplatin in human glioma cells
ترجمه فارسی عنوان
وورتمنین اثر ترکیبی این اتوزوئید و سیس پلاتین را در سلول های گلیوما انسان تقویت می کند
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کلمات کلیدی
CLLXRCC4-like factorXLFXRCC4non-homologous DNA end joiningDNA-PKcsDNA-PKICLNHEJPI3-KATRDSBsPNKDNA double-strand breaks - DNA دو رشته شکستهEtoposide - اتوپوساید، اتوپوزایدionizing radiation - تابش یوننده یا پرتوهای یونیزانATM - خودپردازHuman glioma cells - سلول های انسانی انسانیcisplatin - سیس پلاتینcombination index - شاخص ترکیبیChemosensitization - شیمی درمانیphosphatidylinositol-3-kinase - فسفاتیدیلینواستیل-3-کینازHomologous recombination - نوترکیبی همولوگDNA-dependent protein kinase catalytic subunit - وابسته به DNA وابسته به پروتئین کیناز کاتالیزوریDNA-dependent protein kinase - وابسته به پروتئین کیناز وابسته به DNAwortmannin - ورتمنینpolynucleotide kinase - پولینوکوتید کیناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
The combination of etoposide and cisplatin represents a common modality for treating of glioma patients. These drugs directly and indirectly produce the most lethal DNA double-stand breaks (DSB), which are mainly repaired by non-homologous DNA end joining (NHEJ). Drugs that can specifically inhibit the kinase activity of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), the major component of NHEJ, are of special interest in cancer research. These small molecule inhibitors can effectively enhance the efficacy of current cancer treatments that generate DNA damage. In this study, we investigated the effect of DNA-PKcs inhibitor, wortmannin, on the cytotoxic mechanism of etoposide and cisplatin in MO59K and MO59J human glioblastoma cell lines. These cell lines are proficient and deficient in DNA-PKcs, respectively. Wortmannin synergistically increased the cytotoxicity of cisplatin and etoposide, when combined, in NHEJ-proficient MO59K cells. Surprisingly, wortmannin sensitizing effect was also observed in DNA-PKcs-deficient MO59J cells. These data suggest that wortmannin sensitization to etoposide and cisplatin in human glioma cells is mediated by inhibition of not only DNA-PKcs activity but other enzymes from PI3-K family, e.g. ATM and ATR. A concentration-dependent increase in etoposide and cisplatin-induced DSB levels was potentiated by inhibitor in both cell lines. Moreover, drug-induced accumulation in the G2/M checkpoint and S-phase was increased by wortmannin. Wortmannin significantly inhibited drug-induced DSB repair in MO59 cells and this effect was more pronounced in MO59J cells. We conclude that the mechanism of wortmannin potentiation of etoposide and cisplatin cytotoxicity involves DSBs induction, DSBs repair inhibition, G2/M checkpoint arrest and inhibition of not only DNA-PKcs activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 53, August 2014, Pages 423-431
Journal: The International Journal of Biochemistry & Cell Biology - Volume 53, August 2014, Pages 423-431
نویسندگان
Elzbieta Pastwa, Tomasz Poplawski, Urszula Lewandowska, Stella B. Somiari, Janusz Blasiak, Richard I. Somiari,