کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10903915 1086540 2015 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
C6 ceramide dramatically enhances docetaxel-induced growth inhibition and apoptosis in cultured breast cancer cells: A mechanism study
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
C6 ceramide dramatically enhances docetaxel-induced growth inhibition and apoptosis in cultured breast cancer cells: A mechanism study
چکیده انگلیسی
Here we reported that co-administration of docetaxel and a cell-permeable short-chain ceramide (C6) resulted in a striking increase in growth inhibition and apoptosis in primary and transformed breast cells (MCF-7 and MDA-231), which were associated with mitochondrial permeability transition pore (mPTP) opening, a significant reactive oxygen species (ROS) production and the pro-apoptotic AMP-Protein Kinase (AMPK) as well as c-Jun N-terminal kinases (JNK) activations. Contrarily, the mPTP blocker sanglifehrin A (SfA) or the ROS scavenger N-acetyl-l-cysteine (NAC) largely inhibited co-administration-induced cytotoxicity. Further, cyclosporin A (CsA), the inhibitor of cyclophilin-D (Cyp-D, the key mPTP component), as well as Cyp-D RNA silencing also suppressed breast cancer cell death by the co-treatment, while cells overexpressing Cyp-D showed hypersensitivity to docetaxel. Meanwhile, JNK and AMPK inhibition alleviated cell death induced by the co-administration in cultured breast cancer cells. Significantly, C6 ceramide plus docetaxel caused dramatic human epidermal growth factor receptor (HER)-1/-2 degradation and downstream Akt/Erk inhibition in HER-2 expressing MDA-231 cells. These in vitro findings provide confidence in support of further development of C6 ceramide as an adjunct of docetaxel for the treatment of the metastatic breast cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 332, Issue 1, 1 March 2015, Pages 47-59
نویسندگان
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