Molecular interactions between metformin and D-limonene inhibit proliferation and promote apoptosis in breast and liver cancer cells.

Autor:	Salim EI; Department of Zoology, Research Lab of Molecular Carcinogenesis, Faculty of Science, Tanta University, Tanta, 31527, Egypt. elsayed.salim@science.tanta.edu.eg., Alabasy MM; Department of Zoology, Research Lab of Molecular Carcinogenesis, Faculty of Science, Tanta University, Tanta, 31527, Egypt., Nashar EME; Department of Anatomy, College of Medicine, King Khalid University, Abha, 62529, Saudi Arabia., Al-Zahrani NS; Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, 62529, Saudi Arabia., Alzahrani MA; Internal Medicine Department, College of Medicine, King Khalid University, Abha, 62529, Saudi Arabia., Guo Z; College of Life Science, Center of Bioinformatics, Northwest A and F University, Yangling, Shaanxi, 712100, China., Beltagy DM; Biochemistry Department, Faculty of Science, Damanhour University, Damanhour, Egypt., Shahen M; Department of Zoology, Research Lab of Molecular Carcinogenesis, Faculty of Science, Tanta University, Tanta, 31527, Egypt. Mshahen@science.tanta.edu.eg.
Jazyk:	angličtina
Zdroj:	BMC complementary medicine and therapies [BMC Complement Med Ther] 2024 May 06; Vol. 24 (1), pp. 185. Date of Electronic Publication: 2024 May 06.
DOI:	10.1186/s12906-024-04453-x
Abstrakt:	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: 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: An integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene. 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: 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: 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. (© 2024. The Author(s).)
Databáze:	MEDLINE
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