Molecular interactions between metformin and D-limonene inhibit proliferation and promote apoptosis in breast and liver cancer cells.
D-limonene
Drug–target–pathway network
Gene analysis
HepG2
MCF-7
Metformin
Journal
BMC complementary medicine and therapies
ISSN: 2662-7671
Titre abrégé: BMC Complement Med Ther
Pays: England
ID NLM: 101761232
Informations de publication
Date de publication:
06 May 2024
06 May 2024
Historique:
received:
19
06
2023
accepted:
22
03
2024
medline:
7
5
2024
pubmed:
7
5
2024
entrez:
6
5
2024
Statut:
epublish
Résumé
Cancer is a fatal disease that severely affects humans. Designing new anticancer strategies and understanding the mechanism of action of anticancer agents is imperative. In this study, we evaluated the utility of metformin and D-limonene, alone or in combination, as potential anticancer therapeutics using the human liver and breast cancer cell lines HepG2 and MCF-7. An integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene. We applied a systems-based analysis to introduce a drug-target-pathway network that clarifies different mechanisms of treatment. The combination treatment of metformin and D-limonene induced apoptosis in both cell lines compared with single drug treatments, as indicated by flow cytometric and gene expression analysis. The mRNA expression of Bax and P53 genes were significantly upregulated while Bcl-2, iNOS, and Cox-2 were significantly downregulated in all treatment groups compared with normal cells. The percentages of late apoptotic HepG2 and MCF-7 cells were higher in all treatment groups, particularly in the combination treatment group. Calculations for the combination index (CI) revealed a synergistic effect between both drugs for HepG2 cells (CI = 0.14) and MCF-7 cells (CI = 0.22). Our data show that metformin, D-limonene, and their combinations exerted significant antitumor effects on the cancer cell lines by inducing apoptosis and modulating the expression of apoptotic genes.
Sections du résumé
BACKGROUND
BACKGROUND
Cancer is a fatal disease that severely affects humans. Designing new anticancer strategies and understanding the mechanism of action of anticancer agents is imperative.
HYPOTHESIS/PURPOSE
OBJECTIVE
In this study, we evaluated the utility of metformin and D-limonene, alone or in combination, as potential anticancer therapeutics using the human liver and breast cancer cell lines HepG2 and MCF-7.
STUDY DESIGN
METHODS
An integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene.
METHODS
METHODS
We applied a systems-based analysis to introduce a drug-target-pathway network that clarifies different mechanisms of treatment. The combination treatment of metformin and D-limonene induced apoptosis in both cell lines compared with single drug treatments, as indicated by flow cytometric and gene expression analysis.
RESULTS
RESULTS
The mRNA expression of Bax and P53 genes were significantly upregulated while Bcl-2, iNOS, and Cox-2 were significantly downregulated in all treatment groups compared with normal cells. The percentages of late apoptotic HepG2 and MCF-7 cells were higher in all treatment groups, particularly in the combination treatment group. Calculations for the combination index (CI) revealed a synergistic effect between both drugs for HepG2 cells (CI = 0.14) and MCF-7 cells (CI = 0.22).
CONCLUSION
CONCLUSIONS
Our data show that metformin, D-limonene, and their combinations exerted significant antitumor effects on the cancer cell lines by inducing apoptosis and modulating the expression of apoptotic genes.
Identifiants
pubmed: 38711049
doi: 10.1186/s12906-024-04453-x
pii: 10.1186/s12906-024-04453-x
doi:
Substances chimiques
Metformin
9100L32L2N
Limonene
9MC3I34447
Terpenes
0
Antineoplastic Agents
0
Cyclohexenes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
185Subventions
Organisme : Deanship of Scientific Research at King Khalid University
ID : RGP2/291/44
Informations de copyright
© 2024. The Author(s).
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