کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2000472 1541610 2015 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of endogenous hydrogen sulfide production in clear-cell renal cell carcinoma cell lines and xenografts restricts their growth, survival and angiogenic potential
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Inhibition of endogenous hydrogen sulfide production in clear-cell renal cell carcinoma cell lines and xenografts restricts their growth, survival and angiogenic potential
چکیده انگلیسی


• Levels of hydrogen sulfide (H2S) are elevated in renal cell carcinoma (RCC).
• Inhibiting endogenous H2S production is cytotoxic for RCC cell lines in vitro.
• Inhibiting endogenous H2S production hinders metabolism in VHL-mutant RCC cell lines.
• Inhibiting endogenous H2S production hinders neovascularization of RCC xenografts.

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel–Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H2S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H2S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism and angiogenesis. Using the H2S-specific probe MeRhoAz, it was found that H2S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H2S-producing enzymes could reduce the proliferation, metabolism and survival of ccRCC cell lines, as determined by live-cell imaging, XTT/ATP assay, and flow cytometry respectively. Using the chorioallantoic membrane angiogenesis model, it was found that systemic inhibition of endogenous H2S production was able to decrease vascularization of VHL-deficient ccRCC xenografts. Endogenous H2S production is an attractive new target in ccRCC due to its involvement in multiple aspects of disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nitric Oxide - Volume 49, 15 September 2015, Pages 26–39
نویسندگان
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