Metabolomic Identification of Anticancer Metabolites of Australian Propolis and Proteomic Elucidation of Its Synergistic Mechanisms with Doxorubicin in the MCF7 Cells.
Anti-Infective Agents
/ pharmacology
Antibiotics, Antineoplastic
/ pharmacology
Apoptosis
Breast Neoplasms
/ drug therapy
Cell Proliferation
Doxorubicin
/ pharmacology
Drug Synergism
Drug Therapy, Combination
Female
Humans
MCF-7 Cells
Metabolome
/ drug effects
Propolis
/ pharmacology
Proteome
/ drug effects
MCF7
apoptosis
breast adenocarcinoma
breast cancer
doxorubicin
metabolomics
propolis
proteomics
synergy
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
22 Jul 2021
22 Jul 2021
Historique:
received:
04
06
2021
revised:
18
07
2021
accepted:
19
07
2021
entrez:
7
8
2021
pubmed:
8
8
2021
medline:
17
8
2021
Statut:
epublish
Résumé
The combination of natural products with standard chemotherapeutic agents offers a promising strategy to enhance the efficacy or reduce the side effects of standard chemotherapy. Doxorubicin (DOX), a standard drug for breast cancer, has several disadvantages, including severe side effects and the development of drug resistance. Recently, we reported the potential bioactive markers of Australian propolis extract (AP-1) and their broad spectrum of pharmacological activities. In the present study, we explored the synergistic interactions between AP-1 and DOX in the MCF7 breast adenocarcinoma cells using different synergy quantitation models. Biochemometric and metabolomics-driven analysis was performed to identify the potential anticancer metabolites in AP-1. The molecular mechanisms of synergy were studied by analysing the apoptotic profile via flow cytometry, apoptotic proteome array and measuring the oxidative status of the MCF7 cells treated with the most synergistic combination. Furthermore, label-free quantification proteomics analysis was performed to decipher the underlying synergistic mechanisms. Five prenylated stilbenes were identified as the key metabolites in the most active AP-1 fraction. Strong synergy was observed when AP-1 was combined with DOX in the ratio of 100:0.29 (
Identifiants
pubmed: 34360606
pii: ijms22157840
doi: 10.3390/ijms22157840
pmc: PMC8346082
pii:
doi:
Substances chimiques
Anti-Infective Agents
0
Antibiotics, Antineoplastic
0
Proteome
0
Doxorubicin
80168379AG
Propolis
9009-62-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Western Sydney University
ID : N/A
Organisme : Maxwell Family Foundation
ID : N/A
Organisme : NICM Health Research Institute
ID : N/A
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