This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kessel, D. Articles by Reiners, J. J. Search for Related Content PubMed PubMed Citation Articles by Kessel, D. Articles by Reiners, J. J., Jr.

Potentiation of Photodynamic Therapy by Ursodeoxycholic Acid¹

Departments of Pharmacology and Medicine, Wayne State University School of Medicine [D. K.], and Institute of Chemical Toxicology, Wayne State University [J. A. C., J. J. R.], Detroit, Michigan 48201

Ursodeoxycholic acid (UDCA) protects cells from the apoptotic effects of hydrophobic bile acids and some other cytotoxic agents. We observed the opposite result when assessing the effects of UDCA on the apoptotic response to mitochondrial photodamage induced by photodynamic therapy (PDT). Two photosensitizers with predominantly mitochondrial specificity were used: a porphycene we have designated CPO; and the tin etiopurpurin SnET2. UDCA potentiated the loss of mitochondrial potential, release of cytochrome c into the cytosol, activation of caspase-3, and apoptotic cell death after irradiation of photosensitized murine leukemia L1210 or hepatoma 1c1c7 cells. These effects were not observed when UDCA was added after irradiation. Glyco-UDCA and tauro-UDCA, conjugated forms of UDCA that are formed in vivo, were as effective as UDCA in promoting PDT phototoxicity. Because UDCA does not act by enhancing intracellular accumulation of the photosensitizing agents used in this study, we propose that the mode of action of UDCA involves the sensitization of mitochondrial membranes to photodamage. UDCA is used currently in gastroenterology for several indications. The drug may offer a means for promoting the efficacy of PDT with minimal adverse effects.

This article has been cited by other articles:

				T. Ikegami, Y. Matsuzaki, M. Al Rashid, S. Ceryak, Y. Zhang, and B. Bouscarel Enhancement of DNA topoisomerase I inhibitor-induced apoptosis by ursodeoxycholic acid Mol. Cancer Ther., January 1, 2006; 5(1): 68 - 79. [Abstract] [Full Text] [PDF]

				L. M. Hess, M. F. Krutzsch, J. Guillen, H-H. S. Chow, J. Einspahr, A.K. Batta, G. Salen, M. E. Reid, D. L. Earnest, and D. S. Alberts Results of a Phase I Multiple-Dose Clinical Study of Ursodeoxycholic Acid Cancer Epidemiol. Biomarkers Prev., May 1, 2004; 13(5): 861 - 867. [Abstract] [Full Text] [PDF]

				A. P. Rolo, C. M. Palmeira, J. M. Holy, and K. B. Wallace Role of Mitochondrial Dysfunction in Combined Bile Acid-Induced Cytotoxicity: The Switch Between Apoptosis and Necrosis Toxicol. Sci., May 1, 2004; 79(1): 196 - 204. [Abstract] [Full Text] [PDF]