Original scientific paper
https://doi.org/10.3325/cmj.2025.66.115
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
Ares Alizade
; Department of Medical Pharmacology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey
*
Gulsah Evyapan
; Department of Medical Biology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey
Ibrahim Seyfettin Celik
; Kahramanmaraş Health Services Vocational School, Kahramanmaraş, Turkey
Berna Ozdem
; Department of Medical Biology and Genetics, İnönü University, Malatya, Turkey
* Corresponding author.
Abstract
Aim To investigate the apoptotic and anti-angiogenic ef
fects of metformin in human MCF7 breast cancer cells.
Methods The effect of metformin on cell viability was as
sessed 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 angiogenesis-
and apoptosis-related genes were determined by real
time polymerase chain reaction, Western blot, and flow
cytometry.
Results Metformin reduced the viability and migration of
breast cancer cells compared with the control group. Fur
thermore, metformin (10 μM) increased the apoptosis-re
lated 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 sup
pressed angiogenesis-related genes VEGFA, VEGFR2, and
NRP1.
Conclusions Our results suggest that metformin treat
ment activates apoptosis pathways and inactivates the an
giogenesis pathway. Although this study was conducted
in vitro and did not directly evaluate blood vessel forma
tion, the observed downregulation of angiogenesis-relat
ed genes suggests potential anti-angiogenic activity of
metformin at the gene expression level.
Keywords
Hrčak ID:
352478
URI
Publication date:
23.4.2025.
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