Metformin induces mitochondria-mediated and endoplasmic reticulum stress-mediated apoptosis and inhibits angiogenesis-related gene expression in breast cancer cells via targeting VEGF-A/VEGFR2/NRP1

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dc.contributor.authorAlizade, Ares
dc.contributor.authorEvyapan, Gulsah
dc.contributor.authorCelik, Ibrahim Seyfettin
dc.contributor.authorOzdem, Berna
dc.date.accessioned2026-04-04T13:31:19Z
dc.date.available2026-04-04T13:31:19Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractAim To investigate the apoptotic and anti-angiogenic effects of metformin in human MCF7 breast cancer cells. Methods The effect of metformin on cell viability was assessed by MTS and crystal violet assays, and its effect on cell migration was evaluated by the wound healing assay. The gene expression and protein levels of angiogenesisand apoptosis-related genes were determined by realtime polymerase chain reaction, Western blot, and flow cytometry. Results Metformin reduced the viability and migration of breast cancer cells compared with the control group. Furthermore, metformin (10 mu M) increased the apoptosis-related gene and protein expression of caspase-3, Bax, AIF, CHOP and GRP78 48 hours after treatment compared with the control group. In contrast, it significantly decreased Bcl-2 and Wee1 gene and protein expression and suppressed angiogenesis-related genes VEGFA, VEGFR2, and NRP1. Conclusions Our results suggest that metformin treatment activates apoptosis pathways and inactivates the angiogenesis pathway. Although this study was conducted in vitro and did not directly evaluate blood vessel formation, the observed downregulation of angiogenesis-related genes suggests potential anti-angiogenic activity of metformin at the gene expression level.
dc.identifier.doi10.3325/cmj.2025.66.115
dc.identifier.endpage124
dc.identifier.issn0353-9504
dc.identifier.issn1332-8166
dc.identifier.issue2
dc.identifier.scopus2-s2.0-105005123691
dc.identifier.scopusqualityQ2
dc.identifier.startpage115
dc.identifier.urihttps://doi.org/10.3325/cmj.2025.66.115
dc.identifier.urihttps://hdl.handle.net/11616/108719
dc.identifier.volume66
dc.identifier.wosWOS:001533470800005
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherMedicinska Naklada
dc.relation.ispartofCroatian Medical Journal
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectRisk
dc.titleMetformin induces mitochondria-mediated and endoplasmic reticulum stress-mediated apoptosis and inhibits angiogenesis-related gene expression in breast cancer cells via targeting VEGF-A/VEGFR2/NRP1
dc.typeArticle

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