کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10738013 | 1046678 | 2011 | 17 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Selective targeting of breast cancer cells through ROS-mediated mechanisms potentiates the lethality of paclitaxel by a novel diterpene, gelomulide K
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کلمات کلیدی
PEG-CATPEG-SODPARP-13-ABNACN-acetyl-l-cysteineMDCAVOANI3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide - 3- (4،5-dimethylthiazol-2-yl) -2،5-difenyltetrazolium bromide3-Aminobenzamide - 3-آمینوبنزامیدMTT - MTTROS - ROSAIF - آیفونTrans-stilbene oxide - اکسید Trans-stilbeneFree radicals - رادیکال آزادBreast cancer - سرطان پستانapoptosis-inducing factor - عامل القاء آپوپتوزCaspase-independent cell death - مرگ سلولی مستقل از کاسپازMonodansylcadaverine - مونودانسیل کاداورینPoly(ADP-ribose) polymerase-1 - پلی (ADP-ribose) پلیمراز-1Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Defects in apoptotic pathways confer resistance to tubulin-binding agents via downregulation of caspases or overexpression of antiapoptotic factors, urging the need for novel agents acting on an alternative pathway. The purpose of this study was to investigate whether induction of ROS can induce caspase-independent cell death in breast cancer cells and thereby enhance the activity of paclitaxel. Here, we report that gelomulide K acts as a caspase-independent cell death-inducing agent that synergizes with paclitaxel in breast cancer cells and has low toxicity in normal cells. Treatment with gelomulide K induced PARP-1 hyperactivation, AIF nuclear translocation, and cytoprotective autophagy. These effects were associated with increased ROS production and a decrease in cellular GSH levels in cancer cells. Furthermore, pretreatment with NAC, a precursor of intracellular GSH, effectively abrogated gelomulide K-induced caspase-independent cell death and autophagy, suggesting that ROS-mediated downstream signaling is essential to the anticancer effects of gelomulide K. Additionally, in a xenograft model, gelomulide K induced PARP-1 activation and reduced tumor growth. In terms of structure-activity relationships, analysis not only showed a correlation between ROS levels and drug activity but also highlighted the importance of the 8,14-epoxy group. Taken together, our results show that enhancement of paclitaxel activity can be achieved with gelomulide K and that the structurally relevant pharmacophore provides important insight into the development of new caspase-independent cell death-inducing agents.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 51, Issue 3, 1 August 2011, Pages 641-657
Journal: Free Radical Biology and Medicine - Volume 51, Issue 3, 1 August 2011, Pages 641-657
نویسندگان
Juan-Cheng Yang, Mei-Chin Lu, Chia-Lin Lee, Guan-Yu Chen, Yan-Yu Lin, Fang-Rong Chang, Yang-Chang Wu,