کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10915439 | 1090060 | 2005 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Interactive Effects of HDAC Inhibitors and TRAIL on Apoptosis Are Associated with Changes in Mitochondrial Functions and Expressions of Cell Cycle Regulatory Genes in Multiple Myeloma
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کلمات کلیدی
Z-VAl-Ala-Asp-fluoromethylketoneTSAHDACDCRSAHAIAPPARPz-VAD-fmk - Z-VAD-FMKAIF - آیفونSuberoylanilide hydroxamic acid - اسید سدئروانیلید هیدروکسامTrichostatin A - تریکوستاتین AApoptosis - خزان یاختهایapoptosis-inducing factor - عامل القاء آپوپتوزTRAIL - قطارtumor necrosis factor-related apoptosis-inducing ligand - لیگاند ناشی از آپوپتوز وابسته به عامل بیماری تومورhistone deacetylase inhibitor - مهار کننده هیستون داسیدلازinhibitor of apoptosis protein - مهار کننده پروتئین آپوپتوزیسMultiple myeloma - مولتیپل میلوماhistone deacetylase - هیستون داستیلازPoly(ADP-ribose) polymerase - پلیمر (ADP-ribose) پلیمرازDecoy receptor - گیرنده طعمهdeath receptor - گیرنده مرگDeath receptors - گیرنده های مرگ
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Interactive Effects of HDAC Inhibitors and TRAIL on Apoptosis Are Associated with Changes in Mitochondrial Functions and Expressions of Cell Cycle Regulatory Genes in Multiple Myeloma Interactive Effects of HDAC Inhibitors and TRAIL on Apoptosis Are Associated with Changes in Mitochondrial Functions and Expressions of Cell Cycle Regulatory Genes in Multiple Myeloma](/preview/png/10915439.png)
چکیده انگلیسی
In this study, we have evaluated the cytotoxic effect of combining two HDAC inhibitors, SAHA and TSA, with TRAIL in human multiple myeloma cell lines. Low doses of SAHA or TSA enhanced the cytotoxic and apoptotic effects of TRAIL and upregulated the surface expression of TRAIL death receptors (DR4 and/or DR5). SAHA and TSA induced G1 phase cell cycle growth arrest by upregulating p21WAF1 and p27KiP1 expression and by inhibiting E2F transcriptional activity. The enhanced TRAIL effect after pretreatment with HDAC inhibitors was consistent with the upregulation of the proapoptotic Bcl-2 family members (Bim, Bak, Bax, Noxa, PUMA), the downregulation of the antiapoptotic members of the Bcl-2 family (Bcl-2 and Bcl-XL), IAPs. SAHA and TSA dissipated the mitochondrial membrane potential and enhanced the release of Omi/HtrA2 and AIF from the mitochondria to the cytosol. The cytotoxic effect of both SAHA and TSA was caspase- and calpain-independent. Inhibition of NFÎB activation by the proteasome inhibitor, MG132, enhanced the apoptotic effect of TSA. Our study demonstrated the enhancing effects of HDAC inhibitors on apoptosis when combined with TRAIL and, for the first time, emphasized the role of AIF in mediating the cytotoxic effects of HDAC inhibitors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 7, Issue 7, July 2005, Pages 646-657
Journal: Neoplasia - Volume 7, Issue 7, July 2005, Pages 646-657
نویسندگان
Tamer E. Fandy, Sharmila Shankar, Douglas D. Ross, Edward Sausville, Rakesh K. Srivastava,