کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8434489 1546645 2018 40 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeting the NRF-2/RHOA/ROCK signaling pathway with a novel aziridonin, YD0514, to suppress breast cancer progression and lung metastasis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Targeting the NRF-2/RHOA/ROCK signaling pathway with a novel aziridonin, YD0514, to suppress breast cancer progression and lung metastasis
چکیده انگلیسی
Metastasis is a major cause of breast cancer-associated mortality. Natural products extracted from herbs provide rich bioactive compounds with anticancer efficacy but may have limited or moderate potency and considerable toxicity. We developed a novel aziridonin, YD0514, by aziridinating oridonin, a natural product of the medicinal herb Rabdosia rubescens. In this study, we found that YD0514 significantly inhibited proliferation, motility, and adhesion of metastatic breast cancer cell lines MDA-MB-231, GI101, GILM2, and GILM3. YD0514 also decreased the protein expression of matrix metalloproteinases 2 and 9 (MMP2 and MMP9), focal adhesion kinase (FAK), and integrin family members. Importantly, YD0514 suppressed the growth of metastatic breast cancer xenograft tumors and significantly inhibited lung metastasis in vivo. Lastly, we showed that YD0514's anti-metastatic effect on highly aggressive breast cancer is mediated via regulating the NRF-2/RHOA/ROCK signaling pathway. These results demonstrate that YD0514, the first active analog based on an oridonin D-ring modification, has the potential to be developed as an anti-metastasis therapy for patients with metastatic cancers.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 424, 28 June 2018, Pages 97-108
نویسندگان
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