TY - JOUR TI - Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism AB - Background/aim: In the present study we aimed to figure out the effect of metformin on the expression of AMPK-alpha, cyclin D1, and Tp53, and apoptosis in primary breast cancer cells (PBCCs). Materials and methods: PBCCs were treated with two doses of metformin (0 mM, 25 mM). Proliferation was determined by BrdU assay. Real-time PCR was used to assess AMPK-alpha, cyclin D1, and Tp53 gene expressions; apoptotic indexes of PBCCs were analyzed using flow-cytometry. Results: Twenty-four–hour incubation with 25 mM metformin reduced the proliferation of PBCCs. AMPK-alpha gene expression in PBCCs was not affected by 25 mM metformin treatment compared with the control group. PBCCs treated with 25 mM metformin had lower cyclin D1 expression compared with nontreated cells; however, the difference was not statistically significant. Twenty-five millimolar dose of metformin increased p53 expression significantly compared with the nontreated group. The high concentration of metformin elevated the number of annexin V-positive apoptotic cells, and the increase in the apoptotic index was statistically significant. Conclusion: Metformin can modulate cyclin D1 and p53 expression through AMPK-alpha-independent mechanism in breast cancer cells, leading to cell proliferation inhibition and apoptosis induction.Key words: AMPK-alpha, cyclin D1, Tp53, breast cancer, metformin AU - Hocaoglu-Emre, F Sinem AU - yenmis, guven AU - yaprak saraç, elif AU - BESLI, NAIL AU - Kanıgür-Sultuybek, Gönül AU - Senol, Kazim DO - 10.3906/sag-1908-112 PY - 2021 JO - Turkish Journal of Medical Sciences VL - 51 IS - 2 SN - 1300-0144 SP - 826 EP - 834 DB - TRDizin UR - http://search/yayin/detay/484958 ER -