کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2533468 1559056 2010 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
[Co(III)(cyclen)Cl2]Cl is selectively cytotoxic to human leukaemia cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
[Co(III)(cyclen)Cl2]Cl is selectively cytotoxic to human leukaemia cells
چکیده انگلیسی

Co(III)-cyclen complexes are known to cause DNA strand breaks by hydrolytically cleaving the phosphodiester backbone via a mechanism that does not require oxidation. Here, we report the first cytotoxicity study of [Co(III)(cyclen)Cl2]Cl (2), the parental example of this class of agent, which reveals that (2) is selectively toxic towards CCRF-CEM (IC50 = 32 ± 10 μM), THP-1 (IC50 = 110 ± 40 μM), and HL-60 (IC50 = 70 ± 35 μM) human leukaemia cells, compared to human skin and lung fibroblasts (IC50 > 10 mM). Investigations of its effect on CCRF-CEM cells show it kills by apoptosis which was characterised by microscopy, flow cytometry, and in vitro NMR experiments. The latter involved measurement of the ratio of methylene and methyl 1H resonances at 1.3 and 0.9 ppm, respectively, associated with the externalisation of membrane bound phosphatidyl serine. The NMR data indicate increasing lactate production during apoptosis, which implies involvement of the intrinsic mitochondrial pathway, a notion supported by down-regulation of Bcl-2 and up-regulation of Bax levels as detected by Western blotting.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 637, Issues 1–3, 10 July 2010, Pages 11–15
نویسندگان
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