A Red-Light-Activated Ruthenium-Caged NAMPT Inhibitor Remains Phototoxic in Hypoxic Cancer Cells.

ABSTRACT: We describe two water-soluble ruthenium complexes, [1]Cl2 and [2]Cl2 , that photodissociate to release a cytotoxic nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with a low dose (21?J?cm-2 ) of red light in an oxygen-independent manner. Using a specific NAMPT activity assay, up to an 18-fold increase in inhibition potency was measured upon red-light activation of [2]Cl2 , while [1]Cl2 was thermally unstable. For the first time, the dark and red-light-induced cytotoxicity of these photocaged compounds could be tested under hypoxia (1?% O2 ). In skin (A431) and lung (A549) cancer cells, a 3- to 4-fold increase in cytotoxicity was found upon red-light irradiation for [2]Cl2 , whether the cells were cultured and irradiated with 1?% or 21?% O2 . These results demonstrate the potential of photoactivated chemotherapy for hypoxic cancer cells, in which classical photodynamic therapy, which relies on oxygen activation, is poorly efficient.

SUBMITTER: Lameijer LN 

PROVIDER: S-EPMC5601216 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other