Synergistic effect of dichloroacetate on talaporfin sodium-based photodynamic therapy on U251 human astrocytoma cells.
Dichloroacetate (DCA)
Drug repositioning
Photodynamic therapy ;PDT
Talaporfin sodium (TS)
U251 cells
Journal
Photodiagnosis and photodynamic therapy
ISSN: 1873-1597
Titre abrégé: Photodiagnosis Photodyn Ther
Pays: Netherlands
ID NLM: 101226123
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
13
03
2020
revised:
12
05
2020
accepted:
29
05
2020
pubmed:
5
6
2020
medline:
15
5
2021
entrez:
5
6
2020
Statut:
ppublish
Résumé
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. 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. 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. DCA synergistically enhanced the anti-cancer effect of TS-PDT, illustrating its potential for drug repositioning in cancer therapy in combination with PDT.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
DCA synergistically enhanced the anti-cancer effect of TS-PDT, illustrating its potential for drug repositioning in cancer therapy in combination with PDT.
Identifiants
pubmed: 32497773
pii: S1572-1000(20)30204-0
doi: 10.1016/j.pdpdt.2020.101850
pii:
doi:
Substances chimiques
Photosensitizing Agents
0
Porphyrins
0
Talaporfin
P4ROX5ELT2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101850Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.