کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8301788 | 1537707 | 2016 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Long chain n-3 polyunsaturated fatty acids increase the efficacy of docetaxel in mammary cancer cells by downregulating Akt and PKCε/δ-induced ERK pathways
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کلمات کلیدی
EGFRHP-TLCECLERKEPADMSO - DMSOEicosapentaenoic acid - اسید ایکوزاپنتانوئیکdocosahexaenoic acid - اسید داکوزاگزوائونیکenhanced chemiluminescence - بهبود شیمیایی لومنDHA - دوکوساهگزائنوئیک اسیدdiacylglycerol - دیسیل گلیسیرینDimethyl sulfoxide - دیمتیل سولفواکسیدDAG - روزMEK - مجاهدین خلقCardiolipin - کاردیولیپینhigh performance thin layer chromatography - کروماتوگرافی نازک با عملکرد بالاextracellular signal-related kinase - کیناز مرتبط با سیگنال خارج سلولیEpidermal growth factor receptor - گیرنده فاکتور رشد اپیدرمال
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Long chain n-3 polyunsaturated fatty acids increase the efficacy of docetaxel in mammary cancer cells by downregulating Akt and PKCε/δ-induced ERK pathways Long chain n-3 polyunsaturated fatty acids increase the efficacy of docetaxel in mammary cancer cells by downregulating Akt and PKCε/δ-induced ERK pathways](/preview/png/8301788.png)
چکیده انگلیسی
Taxanes can induce drug resistance by increasing signaling pathways such as PI3K/Akt and ERK, which promote survival and cell growth in human cancer cells. We have previously shown that long chain n-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA, 22:6n-3) decrease resistance of experimental mammary tumors to anticancer drugs. Our objective was to determine whether DHA could increase tumor sensitivity to docetaxel by down-regulating these survival pathways. In docetaxel-treated MDA-MB-231 cells, phosphorylated-ERK1/2 levels were increased by 60% in membrane and nuclear compartments, compared to untreated cells. Our data showed that ERK1/2 activation depended on PKC activation since: i) enzastaurin (a pan-PKC inhibitor) blocked docetaxel-induced ERK1/2 phosphorylation ii) docetaxel increased PKC activity by 30% and phosphatidic acid level by 1.6-fold iii) inhibition of PKCε and PKCδ by siRNA resulted in reduced phosphorylated ERK1/2 levels. In DHA-supplemented cells, docetaxel was unable to increase PKCε and δ levels in membrane and nuclear fractions, resulting in diminished ERK1/2 phosphorylation and increased docetaxel efficacy. Reduced membrane level of PKCε and PKCδ was associated with significant incorporation of DHA in all phospholipids, including phosphatidylcholine which is a major source of phosphatidic acid. Additionally, examination of the Akt pathway showed that DHA could repress docetaxel-induced Ser473Akt phosphorylation. In rat mammary tumors, dietary DHA supplementation during docetaxel chemotherapy repressed ERK and Akt survival pathways and in turn strongly improved taxane efficacy. The P-ERK level was negatively correlated with tumor regression. These findings are of potential clinical importance in treating chemotherapy-refractory cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1861, Issue 4, April 2016, Pages 380-390
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1861, Issue 4, April 2016, Pages 380-390
نویسندگان
Lucie Chauvin, Caroline Goupille, Charly Blanc, Michelle Pinault, Isabelle Domingo, Cyrille Guimaraes, Philippe Bougnoux, Stephan Chevalier, Karine Mahéo,