Synergistic effect of dichloroacetate on talaporfin sodium-based photodynamic therapy on U251 human astrocytoma cells

Abstract

Background: Talaporfin sodium (TS) is an authorized photosensitizer for photodynamic therapy (PDT) against some tumors in Japan; however, the drawbacks of the drug include its high cost and side effects. Thus, reducing the dose of TS in each round of TS-PDT against tumors is important for reducing treatment costs and improving patients' quality of life. Dichloroacetate (DCA) is approved for treating lactic acidosis and hereditary mitochondrial diseases, and it is known to enhance reactive oxygen species production and induce apoptosis in cancer cells. Therefore, DCA has the potential to enhance the effects of TS-PDT and permit the use of lower TS doses without reducing the anti-cancer effect.

Methods: U251 human astrocytoma cells were simultaneously incubated with TS and DCA using different concentrations, administration schedules, and treatment durations, followed by laser irradiation. Cell viability was determined using the CCK-8 assay.

Results: The combinational use of DCA and TS resulted in synergistically enhanced TS-PDT effects in U251 cells. The duration of DCA treatment before TS-PDT slightly enhanced the efficacy of TS-PDT. The intensity of laser irradiation was not associated with the synergistic effect of DCA on TS-PDT. In addition, the relationship between the elapsed time after TS/DCA combination treatment and PDT ineffectiveness was identical to that of TS monotherapy.

Conclusions: DCA synergistically enhanced the anti-cancer effect of TS-PDT, illustrating its potential for drug repositioning in cancer therapy in combination with PDT.

Keywords: Dichloroacetate (DCA); Drug repositioning; Photodynamic therapy ;PDT; Talaporfin sodium (TS); U251 cells.