Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism

Hocaoglu-Emre, F Sinem; yenmis, guven; yaprak saraç, elif; BESLI, NAIL; Kanıgür-Sultuybek, Gönül; Senol, Kazim

doi:10.3906/sag-1908-112

Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism

Güven YENMİŞ, (Biruni Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji Anabilim Dalı, İstanbul, Türkiye)

Nail Beşli, (Sağlık Bilimleri Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji Anabilim Dalı, İstanbul, Türkiye)

Elif YAPRAK SARAÇ, (İstanbul Teknik Üniversitesi, Fen Edebiyat Fakültesi, Moleküler Biyoloji ve Genetik Bölümü, İstanbul, Türkiye)

Fatma Sinem HOCAOĞLU EMRE, (Beykent Üniversitesi, Sağlık Bilimleri Fakültesi, Beslenme ve Diyetetik Bölümü, İstanbul, Türkiye)

Kazım ŞENOL, (Bursa Uludağ Üniversitesi, Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Bursa, Türkiye)

Gönül KANIGÜR SULTUYBEK (İstanbul Aydın Üniversitesi, Tıp Fakültesi, Moleküler Biyoloji ve Genetik Anabilim Dalı, İstanbul, Türkiye)

Turkish Journal of Medical Sciences

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Yıl: 2021 Cilt: 51 Sayı: 2 Sayfa Aralığı: 826 - 834 Metin Dili: İngilizce DOI: 10.3906/sag-1908-112 İndeks Tarihi: 25-01-2022

Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism

Öz:

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

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	yenmis g, BESLI N, yaprak saraç e, Hocaoglu-Emre F, Senol K, Kanıgür-Sultuybek G (2021). Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism. , 826 - 834. 10.3906/sag-1908-112
Chicago	yenmis guven,BESLI NAIL,yaprak saraç elif,Hocaoglu-Emre F Sinem,Senol Kazim,Kanıgür-Sultuybek Gönül Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism. (2021): 826 - 834. 10.3906/sag-1908-112
MLA	yenmis guven,BESLI NAIL,yaprak saraç elif,Hocaoglu-Emre F Sinem,Senol Kazim,Kanıgür-Sultuybek Gönül Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism. , 2021, ss.826 - 834. 10.3906/sag-1908-112
AMA	yenmis g,BESLI N,yaprak saraç e,Hocaoglu-Emre F,Senol K,Kanıgür-Sultuybek G Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism. . 2021; 826 - 834. 10.3906/sag-1908-112
Vancouver	yenmis g,BESLI N,yaprak saraç e,Hocaoglu-Emre F,Senol K,Kanıgür-Sultuybek G Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism. . 2021; 826 - 834. 10.3906/sag-1908-112
IEEE	yenmis g,BESLI N,yaprak saraç e,Hocaoglu-Emre F,Senol K,Kanıgür-Sultuybek G "Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism." , ss.826 - 834, 2021. 10.3906/sag-1908-112
ISNAD	yenmis, guven vd. "Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism". (2021), 826-834. https://doi.org/10.3906/sag-1908-112

APA	yenmis g, BESLI N, yaprak saraç e, Hocaoglu-Emre F, Senol K, Kanıgür-Sultuybek G (2021). Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism. Turkish Journal of Medical Sciences, 51(2), 826 - 834. 10.3906/sag-1908-112
Chicago	yenmis guven,BESLI NAIL,yaprak saraç elif,Hocaoglu-Emre F Sinem,Senol Kazim,Kanıgür-Sultuybek Gönül Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism. Turkish Journal of Medical Sciences 51, no.2 (2021): 826 - 834. 10.3906/sag-1908-112
MLA	yenmis guven,BESLI NAIL,yaprak saraç elif,Hocaoglu-Emre F Sinem,Senol Kazim,Kanıgür-Sultuybek Gönül Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism. Turkish Journal of Medical Sciences, vol.51, no.2, 2021, ss.826 - 834. 10.3906/sag-1908-112
AMA	yenmis g,BESLI N,yaprak saraç e,Hocaoglu-Emre F,Senol K,Kanıgür-Sultuybek G Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism. Turkish Journal of Medical Sciences. 2021; 51(2): 826 - 834. 10.3906/sag-1908-112
Vancouver	yenmis g,BESLI N,yaprak saraç e,Hocaoglu-Emre F,Senol K,Kanıgür-Sultuybek G Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism. Turkish Journal of Medical Sciences. 2021; 51(2): 826 - 834. 10.3906/sag-1908-112
IEEE	yenmis g,BESLI N,yaprak saraç e,Hocaoglu-Emre F,Senol K,Kanıgür-Sultuybek G "Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism." Turkish Journal of Medical Sciences, 51, ss.826 - 834, 2021. 10.3906/sag-1908-112
ISNAD	yenmis, guven vd. "Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism". Turkish Journal of Medical Sciences 51/2 (2021), 826-834. https://doi.org/10.3906/sag-1908-112