Redox active metals and H2O2 mediate the increased efficacy of pharmacological ascorbate in combination with gemcitabine or radiation in pre-clinical sarcoma models.
Redox Biol
; 14: 417-422, 2018 04.
Article
en En
| MEDLINE
| ID: mdl-29069637
ABSTRACT
Soft tissue sarcomas are a histologically heterogeneous group of rare mesenchymal cancers for which treatment options leading to increased overall survival have not improved in over two decades. The current study shows that pharmacological ascorbate (systemic high dose vitamin C achieving ≥ 20mM plasma levels) is a potentially efficacious and easily integrable addition to current standard of care treatment strategies in preclinical models of fibrosarcoma and liposarcoma both in vitro and in vivo. Furthermore, enhanced ascorbate-mediated toxicity and DNA damage in these sarcoma models were found to be dependent upon H2O2 and intracellular labile iron. Together, these data support the hypothesis that pharmacological ascorbate may represent an easily implementable and non-toxic addition to conventional sarcoma therapies based on taking advantage of fundamental differences in cancer cell oxidative metabolism.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ácido Ascórbico
/
Fármacos Sensibilizantes a Radiaciones
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Sarcoma
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Desoxicitidina
/
Peróxido de Hidrógeno
/
Hierro
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Antimetabolitos Antineoplásicos
Límite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
Redox Biol
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos