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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Sodium dichloroacetate attenuates the growth of B16-F10 melanoma in vitro and in vivo: an opportunity for drug repurposing

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Author(s):
do Nascimento, Rodrigo S. [1] ; Nagamine, Marcia K. [1] ; De Toledo, Gabriela F. [1] ; Chaible, Lucas M. [1] ; Tedardi, V, Marcello ; del-Grande, Murilo P. [2] ; da Fonseca, Ivone I. M. [2] ; Dagli, Maria L. Z. [2]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, Lab Expt & Comparat Oncol, Av Prof Dr Orlando Marques de Paiva 87, BR-05508900 Sao Paulo, SP - Brazil
[2] Tedardi, Marcello, V, Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, Lab Expt & Comparat Oncol, Av Prof Dr Orlando Marques de Paiva 87, BR-05508900 Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: ANTI-CANCER DRUGS; v. 32, n. 2, p. 111-116, FEB 2021.
Web of Science Citations: 0
Abstract

Sodium dichloroacetate (DCA) is a metabolic regulator used to treat diabetes. Since DCA inhibits pyruvate dehydrogenase kinase, decreasing lactic acid formation, it can reverse the Warburg effect in cancer cells, promoting apoptosis. Therefore, this study aimed to investigate the potential of DCA as a drug repurposing candidate for the treatment of melanoma. For the in-vitro assay, murine B16-F10 melanoma cells were treated with 0.5, 1, 5, 10, 20 or 50 mM DCA for 3 days, analyzed with the crystal violet method. The in-vivo effect of DCA was evaluated in B16-F10 tumor-bearing C57BL/6 mice treated with different doses of DCA (0, 25, 75 or 150 mg/kg) by gavage for 10 days, followed by measurement of tumor volume. Upon necropsy, representative slices of lung, liver, kidney, spleen and intestine were collected, processed and submitted for histopathological examination. The DCA concentrations of 10, 20 and 50 mM reduced B16-F10 cell viability after 48 and 72 h of treatment, whereas 20 and 50 mM were effective after 24 h of treatment. A significant reduction in tumor growth was observed in B16-F10 melanoma bearing mice at all doses, with no change in body weight or histology. DCA attenuates the growth of B16-F10 melanoma in vitro and in vivo, without systemic toxic effects. Therefore, DCA is a candidate for drug repurposing against melanomas. (AU)

FAPESP's process: 16/20479-7 - Evaluation of the effects of urokinase-activated (uPA) and metalloproteinases (MMPs) toxin on Canine Hemangiosarcoma: in vitro and in vivo studies
Grantee:Márcia Kazumi Nagamine
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 17/12855-1 - Investigation of the carboxyl-terminal Q-connexin peptide (ACT1) activity associated with the inhibitor of histone deacetylases sodium butyrate, and conventional chemotherapeutic agents, on the treatment of canine mammary tumors: in vitro assays.
Grantee:Ivone Izabel Mackowiak da Fonseca
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 14/04819-7 - Investigation of sodium dichloroacetate (DCA) for the treatment of canine neoplasms: in vitro and in vivo preclinical assays
Grantee:Maria Lucia Zaidan Dagli
Support Opportunities: Regular Research Grants
FAPESP's process: 15/01836-0 - Investigation of the effects of sodium dichloroacetate (DCA) on the murine melanoma cells B16/F10
Grantee:Rodrigo Sousa do Nascimento
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/16515-3 - Antineoplastic effects of Dichloroacetate sodium (DCA) and omeprazole (OMP) in canine oral malignant melanoma cell lines: a study of the mechanisms of action
Grantee:Gabriela Fernandes de Toledo
Support Opportunities: Scholarships in Brazil - Master