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Forum on Immunopathological Diseases and Therapeutics

ISSN Print: 2151-8017
ISSN Online: 2151-8025

Forum on Immunopathological Diseases and Therapeutics

DOI: 10.1615/ForumImmunDisTher.v2.i2.50
pages 137-143

Role of RKIP in Sensitizing Tumor Cells to Photodynamic Therapy

Valentina Rapozzi
Department of Biomedical Sciences and Technologies, School of Medicine, University of Udine, Italy
Kazuo Umezawa
Department of Molecular Target Medicine Screening Aichi Medical University School of Medicine, Aichi, Japan
Luigi E. Xodo
Department of Biomedical Sciences and Technologies, School of Medicine, University of Udine, Italy

ABSTRACT

Photodynamic therapy (PDT) combines the administration of a photosensitizer to a tumor and irradiation with nonthermal light to generate cytotoxic reactive oxygen species. The efficacy of the treatment depends on a number of factors including the properties of the photosensitizer, light dosage, and type of the target cells. In general, although PDT is an efficacious treatment modality, in some cases, the risk of recurrence is underestimated; thus, there is interest to improve the activity of PDT. We have recently focused on the photosensitizing properties of pheophorbide a (Pba), a chlorophyll derivative. At high-dose PDT (Pba > IC50), the growth of tumor cells is completely arrested by apoptosis and/or necrosis, while at low dose (Pba < IC50), the photosensitizer causes a temporary growth arrest followed by cell recovery. Because Pba/PDT stimulates, in a dose-dependent manner, the production of nitric oxide (NO) and NO is known to inhibit the NF-κB path-way, which is involved in the NF-κB/Snail/RKIP loop, we evaluated if the tumor cells can be sensitized to PDT by the NO-mediated inhibition of NF-κB and the concomitant activation of the RKIP proapoptotic gene. Our preliminary findings are presented.