Ascorbate sensitizes human osteosarcoma cells to the cytostatic effects of cisplatin.
Antineoplastic Agents
/ pharmacology
Ascorbic Acid
/ administration & dosage
Bone Neoplasms
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cisplatin
/ administration & dosage
Drug Resistance, Neoplasm
/ drug effects
Humans
Osteosarcoma
/ drug therapy
Oxidation-Reduction
/ drug effects
ROS
chemoresistance
metabolism
mitochondria
osteosarcoma
Journal
Pharmacology research & perspectives
ISSN: 2052-1707
Titre abrégé: Pharmacol Res Perspect
Pays: United States
ID NLM: 101626369
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
26
02
2020
revised:
30
06
2020
accepted:
30
06
2020
entrez:
30
7
2020
pubmed:
30
7
2020
medline:
4
6
2021
Statut:
ppublish
Résumé
Osteosarcoma (OS) is the most common malignant bone tumor and a leading cause of cancer-related deaths in children and adolescents. Current standard treatments for OS are a combination of preoperative chemotherapy, surgical resection, and adjuvant chemotherapy. Cisplatin is used as the standard chemotherapeutic for OS treatment, but it induces various adverse effects, limiting its clinical application. Improving treatment efficacy without increasing the cisplatin dosage is desirable. In the present study, we assessed the combined effect of ascorbate on cisplatin treatment using cultured human OS cells. Co-treatment with ascorbate induced greater suppression of OS cell but not nonmalignant cell proliferation. The chemosensitizing effect of ascorbate on cisplatin treatment was tightly linked to ROS production. Altered cellular redox state due to increased ROS production modified glycolysis and mitochondrial function in OS cells. In addition, OS cell sphere formation was markedly decreased, suggesting that ascorbate increased the treatment efficacy of cisplatin against stem-like cells in the cancer cell population. We also found that enhanced MYC signaling, ribosomal biogenesis, glycolysis, and mitochondrial respiration are key signatures in OS cells with cisplatin resistance. Furthermore, cisplatin resistance was reversed by ascorbate. Taken together, our findings provide a rationale for combining cisplatin with ascorbate in therapeutic strategies against OS.
Identifiants
pubmed: 32725721
doi: 10.1002/prp2.632
pmc: PMC7387887
doi:
Substances chimiques
Antineoplastic Agents
0
Ascorbic Acid
PQ6CK8PD0R
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00632Informations de copyright
© 2020 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.
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