کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2131583 | 1086648 | 2009 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3
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کلمات کلیدی
minimal essential medium alphaDMEMMEMαFBSDMHAESI-MSUDP-GlcUART-PCRELSA4-methylumbelliferoneMRM4-MUHBSSPBSHASDulbecco's modified Eagle Medium - Eagle Medium اصلاح شده DulbeccoUDP-glucuronic acid - اسید UDP-گلوکورونیکfetal bovine serum - سرم جنین گاوendoplasmic reticulum - شبکه آندوپلاسمی Phosphate buffered saline - فسفات بافر شورHank's balanced salt solution - محلول نمک متعادل هانکmultiple reaction monitoring - نظارت چندگانه چندگانهHyal - هیالHyaluronan synthase - هیالورونان سنتازHyaluronidase - هیالورونیدازreverse transcriptase polymerase chain reaction - واکنش زنجیره ای پلی مراز ترانس کریتاز معکوسhigh-performance liquid chromatography - کروماتوگرافی مایعی کاراHPLC - کروماتوگرافی مایعی کارا
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3](/preview/png/2131583.png)
چکیده انگلیسی
Hyaluronan accumulation on cancer cells and their surrounding stroma predicts an unfavourable disease outcome, suggesting that hyaluronan enhances tumor growth and spreading. 4-Methylumbelliferone (4-MU) inhibits hyaluronan synthesis and retards cancer spreading in experimental animals through mechanisms not fully understood. These mechanisms were studied in A2058 melanoma cells, MCF-7 and MDA-MB-361 breast, SKOV-3 ovarian and UT-SCC118 squamous carcinoma cells by analysing hyaluronan synthesis, UDP-glucuronic acid (UDP-GlcUA) content, and hyaluronan synthase (HAS) mRNA levels. The maximal inhibition in hyaluronan synthesis ranged 22-80% in the cell lines tested. Active glucuronidation of 4-MU produced large quantities of 4-MU-glucuronide, depleting the cellular UDP-GlcUA pool. The maximal reduction varied between 38 and 95%. 4-MU also downregulated HAS mRNA levels: HAS3 was 84-60% lower in MDA-MB-361, A2058 and SKOV-3 cells. HAS2 was the major isoenzyme in MCF-7 cells and lowered by 81%, similar to 88% in A2058 cells. These data indicate that both HAS substrate and HAS2 and/or HAS3 mRNA are targeted by 4-MU. Despite different target point sensitivities, the reduction of hyaluronan caused by 4-MU was associated with a significant inhibition of cell migration, proliferation and invasion, supporting the importance of hyaluronan synthesis in cancer, and the therapeutic potential of hyaluronan synthesis inhibition.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 315, Issue 11, 1 July 2009, Pages 1914-1923
Journal: Experimental Cell Research - Volume 315, Issue 11, 1 July 2009, Pages 1914-1923
نویسندگان
Anne Kultti, Sanna Pasonen-Seppänen, Marjo Jauhiainen, Kirsi J. Rilla, Riikka Kärnä, Emma Pyöriä, Raija H. Tammi, Markku I. Tammi,