Figure 3. The implications of the bell-shaped pharmacological profile of NO, CO and H2S for the therapy of cancer.
Low concentrations of nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) that are produced endogenously by inducible NO synthase (iNOS), haem oxygenase 1 (HO1) and cystathionine-β-synthase (CBS), respectively, can support tumour growth and tumour angiogenesis through the mediators and effects listed in the green box. Inhibition of these responses (depicted by the red arrow on the left side of the graph) can be of therapeutic benefit, either on its own, or to sensitize the tumour cell to standard anticancer therapies. High concentrations of the gasotransmitters can be cytostatic or cytotoxic; thus, therapeutic administration of each gasotransmitter (depicted by the green arrow on the right side of the graph), to sufficiently high concentrations in the tumour cell can be used to induce anticancer effects (listed in red box) and/or to potentiate anticancer chemo-or radiotherapy. Ticks indicate key pathways or mechanisms involved in the biological actions of low or high levels of each gasotransmitter. Please note that the figure incorporates some generalization; the pathways and mechanisms involved in the action of each gasotransmitter can be dependent on the cell-type and the experimental condition used in the various studies.