Potentiation of photodynamic therapy by ursodeoxycholic acid

Ursodeoxycholic acid (UDCA) protects cells from the apoptotic effects of hy drophobic bile acids and some other cytotoxic agents. We observed the oppos ite result when assessing the effects of UDCA on the apoptotic response to mitochondrial photodamage induced by photodynamic therapy (PDT). Two photos ensitizers with predominantly mitochondrial specificity were used: a porphy cene we have designated CPO; and the tin etiopurpurin SnET2, UDCA potentiat ed the loss of mitochondrial potential, release of cytochrome c into the cy tosol, activation of caspase-3, and apoptotic cell death after irradiation of photosensitized murine leukemia L1210 or hepatoma 1c1c7 cells. These eff ects were not observed when UDCA was added after irradiation. Glyco-UDCA an d tauro-UDCA, conjugated forms of UDCA that are formed in vivo, were as eff ective as UDCA in promoting PDT phototoxicity. Because UDCA does not act by enhancing intracellular accumulation of the photosensitizing agents used I n this study, we propose that the mode of action of UDCA involves the sensi tization 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.