29th Annual Meeting of the American Society of Photobiology

Downtown Marriot

Chicago, Il.

Modulation of Nitric Oxide Levels in Human Cancer Cells Undergoing PDT with Photofrin: Implications for the use of Nitric Oxide in Photodynamic Therapy

Abstract-
Nitric oxide has been reported to play many roles in the biology of cancer. Recent studies have shown that NO may be involved in tumor development, tumor immune responses, metastasis and apoptosis. It has also been demonstrated that NO can modulate the effect of cancer therapies that have an oxidative mechanism. Nitric oxide has been reported to sensitize cells to chemotherapeutic agents that produce reactive oxygen species. Since photodynamic action results in the production of cytotoxic reactive oxygen species, then the modulation of NO in tumor cells during photodynamic therapy could be used to alter oxidative damage. Indeed, when MCF-7 human breast cancer cells were subjected to pretreatment with nitric oxide (as a NO-saturated solution or by NO donors) they were sensitized to PDT with Photofrin. When these same cells were transduced with human iNOS they were also sensitized to PDT with Photofrin. The sensitization was concentration dependent with respect to iNOS protein and activity. Thus, both exogeneously added and endogeneously produced NO can sensitize cells to PDT. Transduction of MCF-7 cells with iNOS leads to the reduction in cellular antioxidant enzyme levels. Transduction of iNOS reduced CAT, MnSOD, and CuZnSOD protein levels and activity. This reduction in the cell's antioxidant enzyme profile may be suggestive as to the mechanism of our observed NO-induced sensitization. These data indicate that modulation of NO in tumors could lead to an increase in the efficacy of PDT and thus better tumor control.

Keywords: antioxidant enzyme, nitric oxide, nitric oxide synthase, photodynamic therapy