Regulation of nadph-dependent nitric oxide and reactive oxygen species signalling in endothelial and melanoma cells by a photoactive nadph analogue
(2014) OncoTarget — Vol. 5, n° 21, p. 10650-10664 (2014)
Files
No attached file found for this publication.
Details
- Authors
- Abstract
- Nitric Oxide (NO) and Reactive oxygen species (ROS) are endogenous regulators of angiogenesis-related events as endothelial cell proliferation and survival, but NO/ROS defect or unbalance contribute to cancers. We recently designed a novel photoactive inhibitor of NO-Synthases (NOS) called NS1, which binds their NADPH site in vitro. Here, we show that NS1 inhibited NO formed in aortic rings. NS1-induced NO decrease led to an inhibition of angiogenesis in a model of VEGF-induced endothelial tubes formation. Beside this effect, NS1 reduced ROS levels in endothelial and melanoma A375 cells and in aorta. In metastatic melanoma cells, NS1 first induced a strong decrease of VEGF and blocked melanoma cell cycle at G2/M. NS1 decreased NOX4 and ROS levels that could lead to a specific proliferation arrest and cell death. In contrast, NS1 did not perturb melanocytes growth. Altogether, NS1 revealed a possible cross-talk between eNOS- and NOX4-associated pathways in melanoma cells via VEGF, Erk and Akt modulation by NS1 that could be targeted to stop proliferation. NS1 thus constitutes a promising tool that modulates NO and redox stresses by targeting and directly inhibiting eNOS and, at least indirectly, NADPH oxidase(s), with great potential to control angiogenesis.
Citations
Rouaud, F., Romero-Perez, M., Wang, H., Lobysheva, I., Ramassamy, B., Henry, E., Tauc, P., Giacchero, D., Boucher, J.-L., Deprez, E., Rocchi, S., & Slama-Schwok, A. (2014). Regulation of nadph-dependent nitric oxide and reactive oxygen species signalling in endothelial and melanoma cells by a photoactive nadph analogue. OncoTarget, 5(21), 10650-10664. https://hdl.handle.net/2078.5/192167 (Original work published 2014)