ArticleBMC complementary medicine and therapies2024
Molecular interactions between metformin and D-limonene inhibit proliferation and promote apoptosis in breast and liver cancer cells.
Article in BMC complementary medicine and therapies, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Iron oxide nanoparticles co-conjugated with hyaluronic acid and limonene trigger oxidative stress and cell cycle arrest in triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2026Article
- Network toxicology-driven repurposing of metformin for hepatocellular carcinoma: insights from molecular docking and dynamics simulations.Journal of molecular modeling · 2026Article
- Potential Anticancer Effects of Limonene Associated with Reactive Oxygen Species Generation, Apoptosis Induction, and NF-κB Modulation in Papillary Renal Cell Carcinoma: A Preliminary Study.Current developments in nutrition · 2026Article
- Looking at the fraction with Annexin V⁺ and propidium iodide⁺: insights into cell death types from preclinical studies in solid and haematological cancers.Apoptosis : an international journal on programmed cell death · 2026Review
- Evaluation of a multi-component mucoadhesive buccal patch: cytokine-associated inflammatory responses and tissue remodeling in experimental models.Frontiers in immunology · 2026Article
- Limonene alleviated ulcerative colitis via anti-inflammation, anti-oxidation and regulating intestinal microenvironment in vivo and in vitro.Inflammopharmacology · 2025Article
- Applications of Limonene in Neoplasms and Non-Neoplastic Diseases.International journal of molecular sciences · 2025Review
- Essential Oils from Citrus Peels Promote Calcium Overload-Induced Calcicoptosis in U251 Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Antioxidant, Anti-Inflammatory, and Anticancer Activities of Five Citrus Peel Essential Oils.Antioxidants (Basel, Switzerland) · 2024Article
- Rosuvastatin Flexible Chitosomes: Development, In Vitro Evaluation and Enhancement of Anticancer Efficacy Against HepG2 and MCF7 Cell Lines.AAPS PharmSciTech · 2024Article
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Authors and funding
8 authors.
Funding
Abstract
backgroundCancer 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
designAn integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene.
methodsWe 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.
resultsThe 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).
conclusionOur 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.
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