کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10914648 | 1088804 | 2015 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Targeting Nrf2 in healthy and malignant ovarian epithelial cells: Protection versus promotion
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کلمات کلیدی
transcription activator-like effectorZFPNuclear factor erythroid 2-like 2ATFBERPARPkelch like-ECH-associated protein 1EOCkeap1 - buy1CRISPR/Cas9 - CRISPR / Cas9NER - DOWNROS - ROSbase excision repair - تعمیر پایه پایهTALE - تلهOxidative stress - تنش اکسیداتیوEpithelial ovarian cancer - سرطان تخمدان اپیتلیالOvarian carcinogenesis - سرطان زایی تخمدانantioxidant response element - عنصر پاسخ آنتی اکسیدانartificial transcription factor - فاکتور رونویسی مصنوعیPARP inhibitor - مهار کننده PARPHomologous recombination - نوترکیبی همولوگARE - هستندZinc finger protein - پروتئین انگشت رویpoly ADP ribose polymerase - پلی ADA ریبوز پلی مرازBRCA1 - ژن BRCA1Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Targeting Nrf2 in healthy and malignant ovarian epithelial cells: Protection versus promotion Targeting Nrf2 in healthy and malignant ovarian epithelial cells: Protection versus promotion](/preview/png/10914648.png)
چکیده انگلیسی
Risk factors indicate the importance of oxidative stress during ovarian carcinogenesis. To tolerate oxidative stress, cells activate the transcription factor Nrf2 (Nfe2l2), the master regulator of antioxidant and cytoprotective genes. Indeed, for most cancers, hyperactivity of Nrf2 is observed, and siRNA studies assigned Nrf2 as therapeutic target. However, the cancer-protective role of Nrf2 in healthy cells highlights the requirement for an adequate therapeutic window. We engineered artificial transcription factors to assess the role of Nrf2 in healthy (OSE-C2) and malignant ovarian cells (A2780). Successful NRF2 up- and downregulation correlated with decreased, respectively increased, sensitivity toward oxidative stress. Inhibition of NRF2 reduced the colony forming potential to the same extent in wild-type and BRCA1 knockdown A2780 cells. Only in BRCA1 knockdown A2780 cells, the effect of Nrf2 inhibition could be enhanced when combined with PARP inhibitors. Therefore, we propose that this combination therapy of PARP inhibitors and Nrf2 inhibition can further improve treatment efficacy specifically in BRCA1 mutant cancer cells without acquiring the side-effects associated with previously studied Nrf2 inhibition combinations with either chemotherapy or radiation. Our findings stress the dual role of Nrf2 in carcinogenesis, while offering approaches to exploit Nrf2 as a potent therapeutic target in ovarian cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Oncology - Volume 9, Issue 7, August 2015, Pages 1259-1273
Journal: Molecular Oncology - Volume 9, Issue 7, August 2015, Pages 1259-1273
نویسندگان
Monique G.P. van der Wijst, Christian Huisman, Archibold Mposhi, Gerard Roelfes, Marianne G. Rots,