Enhanced Antitumor Activity against Melanoma Cancer Cells by Nitric Oxide Release and Photosensitized Generation of Singlet Oxygen from Ruthenium Complexes

Abstract

We have investigated the synergistic effect of nitric oxide and singlet oxygen originating from stimulated ruthenium complexes and their photodynamic action against a melanoma cancer cell line. In aqueous solution, the photosensitizer [Ru(NH3)5pz]2+(I; pz = pyrazine) and the nitrosylruthenium complex trans-[RuCl([15]aneN4)NO]2+(II; [15]aneN4= 1,4,8,12-tetrazacyclopentadecane) can produce singlet oxygen and nitric oxide, respectively. The phototoxicity of complex I does not correlate with the singlet oxygen quantum yields unless it is mediated by nitric oxide release from complex II. This effect is around 70 and 50 % higher than the effect prompted by compounds I and II, respectively, in isolation in the presence of light. It was found that the number of hypodiploid cells in the melanoma cancer cells increased, which indicates that a mixture of compounds I and II induces apoptosis of tumorigenic cell lines. Both singlet oxygen and nitric oxide produced by the ruthenium complexes enhance the photodynamic efficacy in melanoma cancer cells.