Inhibition of endogenous hydrogen sulfide production in clear-cell renal cell carcinoma cell lines and xenografts restricts their growth, survival and angiogenic potential

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

Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society 2015 Jun 09 [Epub]

Eric Sonke, Megan Verrydt, Carl O Postenka, Siddika Pardhan, Chantalle J Willie, Clarisse R Mazzola, Matthew D Hammers, Michael D Pluth, Ian Lobb, Nicholas E Power, Ann F Chambers, Hon S Leong, Alp Sener

Department of Anatomy & Cell Biology, Schulich Medicine and Dentistry, Medical Sciences Building Room 443, Western University, London, Ontario N6A 5C1, Canada; Matthew Mailing Centre for Translational Transplant Studies, 339 Windermere Rd , London Health Sciences Centre, London, Ontario N6A 5A5, Canada Electronic address: esonke@uwo ca , Matthew Mailing Centre for Translational Transplant Studies, 339 Windermere Rd , London Health Sciences Centre, London, Ontario N6A 5A5, Canada; Department of Biology, 1151 Richmond St , Western University, London, Ontario N6A 5B7, Canada Electronic address: mverrydt@uwo ca , London Regional Cancer Program, 790 Commissioners Rd E, London Health Sciences Centre, London, Ontario N6A 5A5, Canada Electronic address: cpostenk@uwo ca , Department of Surgery, Schulich Medicine and Dentistry, 268 Grosvenor St , St Joseph's Hospital, London, Ontario N6A 4V2, Canada; Translational Prostate Cancer Research Laboratory, F3-124, 268 Grosvenor St , St Joseph's Hospital, London, Ontario N6A 4V2, Canada Electronic address: siddika 15@gmail com , Department of Surgery, Schulich Medicine and Dentistry, 268 Grosvenor St , St Joseph's Hospital, London, Ontario N6A 4V2, Canada; Translational Prostate Cancer Research Laboratory, F3-124, 268 Grosvenor St , St Joseph's Hospital, London, Ontario N6A 4V2, Canada Electronic address: chantalle willie@gmail com , Department of Surgery, Schulich Medicine and Dentistry, 268 Grosvenor St , St Joseph's Hospital, London, Ontario N6A 4V2, Canada Electronic address: mazzola_clarisse@hotmail fr , Department of Chemistry & Biochemistry, 1253 University of Oregon, University of Oregon, Eugene, OR 97403, USA Electronic address: mhammers@uoregon edu , Department of Chemistry & Biochemistry, 1253 University of Oregon, University of Oregon, Eugene, OR 97403, USA Electronic address: pluth@uoregon edu , Matthew Mailing Centre for Translational Transplant Studies, 339 Windermere Rd , London Health Sciences Centre, London, Ontario N6A 5A5, Canada; Department of Microbiology and Immunology, Schulich Medicine and Dentistry, Dental Sciences Building Room 3014, Western University, London, Ontario N6A 5C1, Canada; Schulich School of Medicine and Dentistry, Clinical Skills Building, Western University, London, Ontario N6A 5C1, Canada Electronic address: ilobb@uwo ca , Department of Surgery, Schulich Medicine and Dentistry, 268 Grosvenor St , St Joseph's Hospital, London, Ontario N6A 4V2, Canada; Department of Oncology, Schulich Medicine and Dentistry, 790 Commissioners Rd E Room A4901, London Regional Cancer Program, London, Ontario N6A 4L6, Canada Electronic address: nicholas power@lhsc on ca , London Regional Cancer Program, 790 Commissioners Rd E, London Health Sciences Centre, London, Ontario N6A 5A5, Canada; Department of Oncology, Schulich Medicine and Dentistry, 790 Commissioners Rd E Room A4901, London Regional Cancer Program, London, Ontario N6A 4L6, Canada Electronic address: ann chambers@lhsc on ca , Department of Surgery, Schulich Medicine and Dentistry, 268 Grosvenor St , St Joseph's Hospital, London, Ontario N6A 4V2, Canada; Translational Prostate Cancer Research Laboratory, F3-124, 268 Grosvenor St , St Joseph's Hospital, London, Ontario N6A 4V2, Canada; Department of Microbiology and Immunology, Schulich Medicine and Dentistry, Dental Sciences Building Room 3014, Western University, London, Ontario N6A 5C1, Canada Electronic address: hon leong@lhsc on ca , Matthew Mailing Centre for Translational Transplant Studies, 339 Windermere Rd , London Health Sciences Centre, London, Ontario N6A 5A5, Canada; Department of Surgery, Schulich Medicine and Dentistry, 268 Grosvenor St , St Joseph's Hospital, London, Ontario N6A 4V2, Canada; Department of Microbiology and Immunology, Schulich Medicine and Dentistry, Dental Sciences Building Room 3014, Western University, London, Ontario N6A 5C1, Canada; Schulich School of Medicine and Dentistry, Clinical Skills Building, Western University, London, Ontario N6A 5C1, Canada; Multiorgan Transplant Program, 339 Windermere Rd , London Health Sciences Centre, London, Ontario N6A 5A5, Canada  

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