کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2515134 1118502 2007 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mechanism of acridine-based telomerase inhibition and telomere shortening
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Mechanism of acridine-based telomerase inhibition and telomere shortening
چکیده انگلیسی

The trisubstituted acridine compound BRACO-19 has been developed as a ligand for stabilising G-quadruplex structures. It is shown here that BRACO-19 produces short- and long-term growth arrest in cancer cell lines, and is significantly less potent in a normal cell line. BRACO-19 reduces telomerase activity and long-term telomere length attrition is observed. It is also shown that BRACO-19 binds to telomeric single-stranded overhang DNA, consistent with quadruplex formation, and the single-stranded protein hPOT1 has been shown to be displaced from the overhang in vitro and in cellular experiments. It is concluded that the cellular activity of BRACO-19 can be ascribed both to the uncapping of 3′ telomere ends and to telomere shortening that may preferentially affect cells with short telomeres.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 74, Issue 5, 1 September 2007, Pages 679–689
نویسندگان
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