کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5860001 1133162 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Arsenic trioxide suppresses transcription of hTERT through down-regulation of multiple transcription factors in HL-60 leukemia cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Arsenic trioxide suppresses transcription of hTERT through down-regulation of multiple transcription factors in HL-60 leukemia cells
چکیده انگلیسی
Acute promyelocytic leukemia (APL) is largely caused by the t(15,17) chromosome translocation, leading to the production of the PML/retinoic acid receptor alpha fusion. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), as a monotherapy or combination therapy, have been successfully used to treat APL primarily by targeting the degradation of the fusion protein. We previously observed that ATO treatment induced cell death in APL cell line HL-60 accompanied by inhibition of the human telomere reverse transcriptase (hTERT) activity, a critical enzyme responsible for the control of cell replication and transformation in cancer cells. In the present study, we investigated the underlying mechanism by which hTERT activity is inhibited by ATO in HL-60 cells. Our results showed that ATO down-regulated the expression of hTERT at both mRNA and protein levels. Further molecular analysis revealed that the expression of four transcription factors Sp1, c-Myc, NF-κB and USF2, which are located in the proximate promoter region (−1126 to −47) of hTERT, was also suppressed by ATO. Notably, we observed that down-regulation of these four factors by their siRNAs potentiates ATO-induced cell growth inhibition and apoptosis. Therefore, our results provide a novel mechanism of action of ATO for the treatment of APL.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 232, Issue 2, 22 January 2015, Pages 481-489
نویسندگان
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