Promotion of PDT efficacy by bile acids

We previously described the ability of the bile acid UDCA (ursodeoxycholic acid) to enhance the efficacy of photodynamic therapy by promoting the apoptotic response to photodamage. Further studies have now revealed that this effect occurs only when the target for photodamage is the anti-apoptotic protein Bcl-2. The efficacy of lysosomal photodamage, leading to a cleavage of the protein Bid, is not influenced by UDCA. Moreover, apoptotic cell death resulting from treatment of cells with the non-peptidic Bcl-2 inhibitor HA 14-1 is also promoted by UDCA. These results are consistent with the hypothesis that the pro-apoptotic effects of UDCA are specifically directed against Bcl-2, enhancing binding of HA 14-1 and promoting sensitivity of Bcl-2 to photodamage.