Reversing Reprogramming of Cancer Cell Metabolism by Singlet Oxygen Triggered Release of Dichloroacetate Enhances Photodynamic Cytotoxicity

Cancer cells change their glucose metabolism towards lactic acid production for various defensive and proliferative advantages.  Dichloroacetate (DCA) is an inhibitor of a key enzyme and thus, changes back the OX-PHOS to glycolysis ratio.  We designed and synthesized a singlet oxygen triggered source of dichloroacetate which releases this inhibitor during photodynamic singlet oxygen generation.  Synergistic action of DCA and singlet oxygen results in significant enhancement of photocytotoxicity.  The results suggest that this approach could offer significant improvement in the therapeutic outcome of PDT.