Pharmacological Inhibition of Endogenous Hydrogen Sulfide Production Slows Bladder Cancer Progression in an Intravesical Murine Model

Sydney Relouw; George J. Dugbartey; Patrick McLeod; Natasha N. Knier; Francisco Martinez Santiesteban; Paula J. Foster; Heather-Anne Cadieux-Pitre; Nicole M. Hague; Jenna Caine; Kaitlin Belletti; Sally Major; Caroline O’Neil; Manal Y. Gabril; Madeleine Moussa; Melissa J. Huynh; S.M. Mansour Haeryfar; Alp Sener

doi:10.3390/ph17091212

Pharmaceuticals (Sep 2024)

Pharmacological Inhibition of Endogenous Hydrogen Sulfide Production Slows Bladder Cancer Progression in an Intravesical Murine Model

Sydney Relouw,
George J. Dugbartey,
Patrick McLeod,
Natasha N. Knier,
Francisco Martinez Santiesteban,
Paula J. Foster,
Heather-Anne Cadieux-Pitre,
Nicole M. Hague,
Jenna Caine,
Kaitlin Belletti,
Sally Major,
Caroline O’Neil,
Manal Y. Gabril,
Madeleine Moussa,
Melissa J. Huynh,
S.M. Mansour Haeryfar,
Alp Sener

Affiliations

Sydney Relouw: Department of Microbiology & Immunology, Western University, London, ON N6A 5C1, Canada
George J. Dugbartey: Matthew Mailing Center for Translational Transplant Studies, Western University, London Health Sciences Center, London, ON N6A 5A5, Canada
Patrick McLeod: Matthew Mailing Center for Translational Transplant Studies, Western University, London Health Sciences Center, London, ON N6A 5A5, Canada
Natasha N. Knier: Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada
Francisco Martinez Santiesteban: Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada
Paula J. Foster: Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada
Heather-Anne Cadieux-Pitre: Department of Animal Care & Veterinary Services, Western University, London, ON N6A 5C1, Canada
Nicole M. Hague: Department of Animal Care & Veterinary Services, Western University, London, ON N6A 5C1, Canada
Jenna Caine: Department of Animal Care & Veterinary Services, Western University, London, ON N6A 5C1, Canada
Kaitlin Belletti: Department of Animal Care & Veterinary Services, Western University, London, ON N6A 5C1, Canada
Sally Major: Matthew Mailing Center for Translational Transplant Studies, Western University, London Health Sciences Center, London, ON N6A 5A5, Canada
Caroline O’Neil: Robarts Research Institute, Western University, London, ON N6A 3K7, Canada
Manal Y. Gabril: Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 5C1, Canada
Madeleine Moussa: Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 5C1, Canada
Melissa J. Huynh: Department of Surgery, Western University, London, ON N6A 5C1, Canada
S.M. Mansour Haeryfar: Department of Microbiology & Immunology, Western University, London, ON N6A 5C1, Canada
Alp Sener: Department of Microbiology & Immunology, Western University, London, ON N6A 5C1, Canada

DOI: https://doi.org/10.3390/ph17091212
Journal volume & issue: Vol. 17, no. 9
p. 1212

Abstract

Read online

Present bladder cancer therapies have relatively limited therapeutic impact and account for one of the highest lifetime treatment costs per patient. Therefore, there is an urgent need to explore novel and optimized treatment strategies. The present study investigated the effects of inhibiting endogenous hydrogen sulfide (H2S) production on bladder cell viability and in vivo tumor progression. We targeted the H2S-producing enzyme, cystathionine γ-lyase, in 5637 cells using propargylglycine (H2S inhibitor) and performed cytofluorimetric analysis to evaluate cell viability. We then tested the efficacy of propargylglycine alone or in combination with gemcitabine (conventional chemotherapy) in an intravesical murine model of bladder cancer. Magnetic resonance imaging and immunohistochemical staining for cell proliferation, apoptosis, immune-cell infiltration, and neovascularization were performed to evaluate tumor response. Compared to control conditions or cohorts, propargylglycine administration significantly attenuated bladder cancer cell viability in vitro (p p p p + T cell (p + macrophage (p p p 2S production can be protective against bladder cancer by enhancing the chemotherapeutic action of gemcitabine and may be a novel pharmacological target and approach for improved bladder cancer diagnosis and treatments in the future.

Published in Pharmaceuticals

ISSN: 1424-8247 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Pharmacy and materia medica
Website: http://www.mdpi.com/journal/pharmaceuticals/

About the journal

Abstract

Keywords