کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9001991 | 1118566 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cell apoptosis induced by a synthetic carbazole compound LCY-2-CHO is mediated through activation of caspase and mitochondrial pathways
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کلمات کلیدی
GSHNACzVAD-fmkzIETD-fmkZ-VAl-Ala-Asp-fluoromethylketoneROS - ROSApoptosis - خزان یاختهایlactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH Mitochondria - میتوکندریاN-acetyl cysteine - نیتستیل سیستئینCaspases - کاسپازCarbazole - کربازولGlutathione - گلوتاتیونReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Cell apoptosis induced by a synthetic carbazole compound LCY-2-CHO is mediated through activation of caspase and mitochondrial pathways Cell apoptosis induced by a synthetic carbazole compound LCY-2-CHO is mediated through activation of caspase and mitochondrial pathways](/preview/png/9001991.png)
چکیده انگلیسی
The mechanisms involved in the apoptotic effect of LCY-2-CHO [9-(2-chlorobenzyl)-9H-carbazole-3-carbaldehyde], a synthetic carbazole derivative identified as an anti-inflammatory compound, were studied. Cell cycle analysis by propidium iodide staining in human THP-1 monocytic leukemia cells showed the ability of LCY-2-CHO to increase cell population in sub-G1 stage with time- and concentration-dependent manners. LCY-2-CHO-mediated cell death was also demonstrated by DNA laddering and was not related to the release of lactate dehydrogenase. Apoptosis in THP-1 cells induced by LCY-2-CHO was accompanied by the Bid cleavage, collapse of mitochondrial transmembrane potential, the release of cytochrome c and the activation of caspase-3. The apoptotic effect of LCY-2-CHO was diminished by the presence of zVEID-fmk (caspase-6 inhibitor), zIETD-fmk (caspase-8 inhibitor), and zVAD-fmk (non-selective caspase inhibitor), but was not altered by several antioxidants, and cathepsin inhibitor. The Bid cleavage and loss of mitochondrial transmembrane potential, but not the cytochrome c release, were reversed by zIETD-fmk. Comparing the cell selectivity of LCY-2-CHO, we found T-cell acute lymphoblastic CEM leukemia cells were sensitive to 1 μM LCY-2-CHO, acute myeloid leukemia HL-60 cells underwent apoptosis at 10 μM, while adherent cancer cells, such as PC3, HT29 and MCF-7, were resistant to 30 μM LCY-2-CHO within 24-h incubation. Taken together in the present study, we demonstrated LCY-2-CHO might be apoptotic for malignant hematopoietic cells but not anchorage-dependent cells. This action is mediated by an intrinsic caspase-dependent apoptotic event involving mitochondria.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 70, Issue 1, 1 July 2005, Pages 102-112
Journal: Biochemical Pharmacology - Volume 70, Issue 1, 1 July 2005, Pages 102-112
نویسندگان
Ming-Jen Hsu, Yee Chao, Ying-Hsin Chang, Feng-Ming Ho, Li-Jiau Huang, Ya-Ling Huang, Tien-Yau Luh, Chih-Ping Chen, Wan-Wan Lin,