کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8325143 | 1539930 | 2011 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A novel PKC-ι inhibitor abrogates cell proliferation and induces apoptosis in neuroblastoma
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کلمات کلیدی
CDKPKC-ιCAKCDK7PARPPKCDAPIDPBSMBP4′, 6-diamidino-2-phenylindole - 4 '، 6-دیامیدینو-2-فنیلینولshort interfering RNA - RNA تداخل کوتاهsiRNA - siRNAEDTA - اتیلن دی آمین تترا استیک اسید Ethylenediaminetetraacetic acid - اتیلینیدامین تتراستیک اسیدProliferation - ترویجTUNEL - تونلApoptosis - خزان یاختهایNeuroblastoma - نوروبلاستوماMyelin basic protein - پروتئین پایه میلینProtein kinase C - پروتئین کیناز سیpoly (ADP-ribose) polymerase - پلی (ADP-ribose) پلیمرازCaspases - کاسپازcyclin dependent kinase - کییناز وابسته به کیناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A novel PKC-ι inhibitor abrogates cell proliferation and induces apoptosis in neuroblastoma A novel PKC-ι inhibitor abrogates cell proliferation and induces apoptosis in neuroblastoma](/preview/png/8325143.png)
چکیده انگلیسی
Protein Kinase C-iota (PKC-ι), an atypical protein kinase C isoform manifests its potential as an oncogene by targeting various aspects of cancer cells such as growth, invasion and survival. PKC-ι confers resistance to drug-induced apoptosis in cancer cells. The acquisition of drug resistance is a major obstacle to good prognosis in neuroblastoma. The focus of this research was to identify the efficacy of [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate (ICA-1) as a novel PKC-ι inhibitor in neuroblastoma cell proliferation and apoptosis. ICA-1 specifically inhibits the activity of PKC-ι but not that of PKC-zeta (PKC-ζ), the closely related atypical PKC family member. The IC50 for the kinase activity assay was approximately 0.1 μM which is 1000 times less than that of aurothiomalate, a known PKC-ι inhibitor. Cyclin dependent kinase 7 (Cdk7) phosphorylates cyclin dependent kinases (cdks) and promotes cell proliferation. Our data shows that PKC-ι is an in vitro Cdk7 kinase and the phosphorylation of Cdk7 by PKC-ι was potently inhibited by ICA-1. Furthermore, our data shows that neuroblastoma cells proliferate via a PKC-ι/Cdk7/cdk2 cell signaling pathway and ICA-1 mediates its antiproliferative effects by inhibiting this pathway. ICA-1 (0.1 μM) inhibited the in vitro proliferation of BE(2)-C neuroblastoma cells by 58% (P = 0.01). Additionally, ICA-1 also induced apoptosis in neuroblastoma cells. Interestingly, ICA-1 did not affect the proliferation of normal neuronal cells suggesting its potential as chemotherapeutic with low toxicity. Hence, our results emphasize the potential of ICA-1 as a novel PKC-ι inhibitor and chemotherapeutic agent for neuroblastoma.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 43, Issue 5, May 2011, Pages 784-794
Journal: The International Journal of Biochemistry & Cell Biology - Volume 43, Issue 5, May 2011, Pages 784-794
نویسندگان
Prajit Pillai, Shraddha Desai, Rekha Patel, Mini Sajan, Robert Farese, David Ostrov, Mildred Acevedo-Duncan,