Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells.
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Cisplatin
/ administration & dosage
Diterpenes, Kaurane
/ administration & dosage
Dose-Response Relationship, Drug
Drug Synergism
Esophageal Neoplasms
/ pathology
Esophageal Squamous Cell Carcinoma
/ pathology
Glutathione
/ drug effects
Humans
Inhibitory Concentration 50
Reactive Oxygen Species
/ metabolism
Signal Transduction
/ drug effects
Tumor Suppressor Protein p53
/ drug effects
Journal
Anti-cancer drugs
ISSN: 1473-5741
Titre abrégé: Anticancer Drugs
Pays: England
ID NLM: 9100823
Informations de publication
Date de publication:
01 01 2022
01 01 2022
Historique:
pubmed:
15
9
2021
medline:
5
3
2022
entrez:
14
9
2021
Statut:
ppublish
Résumé
Oridonin (ORI) is known to pose anticancer activity against cancer, which could induce the therapeutic impact of chemotherapy drugs. However, such simple combinations have numerous side effects such as higher toxicity to normal cells and tissues. To enhance the therapeutic effects with minimal side effects, here we used ORI in combination with cisplitin (CIS) against different esophageal squamous cell carcinoma (ESCC) cell lines in vitro, to investigate the synergistic anticancer effects of the two drugs against ESCC. Calcusyn Graphing Software was used to assess the synergistic effect. Apoptosis, wound healing and cell invasion assay were conducted to further confirm the synergistic effects of ORI and CIS. Intracellular glutathione (GSH) and reactive oxygen species assay, immunofluorescence staining and western blot were used to verify the mechanism of synergistic cytotoxicity. ORI and CIS pose selective synergistic effects on ESCC cells with p53 mutations. Moreover, we found that the synergistic effects of these drugs are mediated by GSH/ROS systems, such that intracellular GSH production was inhibited, whereas the ROS generation was induced following ORI and CIS application. In addition, we noted that DNA damage was induced as in response to ORI and CIS treatment. Overall, these results suggest that ORI can synergistically enhance the effect of CIS, and GSH deficiency and p53 mutation, might be biomarkers for the combinational usage of ORI and CIS.
Identifiants
pubmed: 34520434
doi: 10.1097/CAD.0000000000001237
pii: 00001813-202201000-00059
pmc: PMC8670348
doi:
Substances chimiques
Diterpenes, Kaurane
0
Reactive Oxygen Species
0
Tumor Suppressor Protein p53
0
oridonin
0APJ98UCLQ
Glutathione
GAN16C9B8O
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e444-e452Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
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