Abstract
The gasotransmitter hydrogen sulfide (H2S) is endogenously produced by three enzymes. One of which, cystathionine beta-synthase has been shown to be upregulated in cancer of the colon, ovary and breast and satisfies the increased metabolic demands of these tumours, in addition to facilitating proliferation and angiogenesis. Catabolism of H2S has been shown to fuel ATP production in hypoxic cells, therefore it is our hypothesis that H2S production is enhanced in hypoxia-signalling renal cell carcinoma (RCC) tumours, and contributes to tumour growth and vascularization. The viability and proliferation of two RCC cell lines (786-O and 769-P) were examined in vitro and in an avian xenograft model. In vitro, cells were cultured in either normoxia (21% O2) or hypoxia (1% O2) and treated with inhibitors of H2S synthesis (hydroxylamine (HA) and propargyl glycine (PAG)), a substrate for H2S synthesis ( l -cysteine), and an H2S-donor molecule (GYY-4137). Similar treatments were administered to xenografted tumours in vivo, followed by imaging to assess changes in tumour volume/vascularization. Both RCC cell lines displayed declines in viability and proliferation when treated with HA (p l -cysteine/GYY-4137 in combination improved hypoxic viability (p The mechanisms behind H2S-mediated proliferation and angiogenesis are unknown, although these results warrant further investigation in the context of RCC.
Published Version
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