The role of nitric oxide in Photodynamic Therapy of cancer

DI VENOSA G, PEROTTI C, FUKUDA H, CASAS A, BATLLE A.

Londres, Inglaterra

Congreso; BMLA Autumn Meeting London; 2004

British Medical Laser Association

Photodynamic Therapy (PDT) is a promising treatment for superficial tumors which involves photosensitization of a molecule upon light exposure. In the present work we employed 5-aminolevulinic acid (ALA) as natural precursor of porphyrins. Porphyrins are excellent photosensitizers and, upon light induction, oxygen species are generated and subcellular targets are attacked. The aim of this work was study the interaction of nitric oxide (NO), which is a messenger and a highly reactive molecule, with ALA-PDT. Weemployed 3 murine mammary adenocarcinoma cell lines: LM2 (non NO producer), LM3 (NO producer) and SNP-LM3 (subline derived from LM3 and resistant to the NO donor sodium nitroprusside (SNP)). We found that LM3 cells are the most resistant to ALA-PDT, whereas LM3-SNP are more sensitive and LM2 even more (lethal light doses 50: 0.27 J/cm2 for LM3, 0.10 for LM3-SNP y 0.047 for LM2). We also observed that SNP protected the 3 lines from photodynamic damage, which was correlated with a strong impairment of porphyrin synthesis. However, endogenous induction of NO generated by arginine exposure, did not modify either porphyrin synthesis or PDT response. On the other hand, ALA treatment induces NO release from SNP both in cells and incubation media. These results suggest that NO levels could modify sensitivity to ALA-PDT.