Page 97 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

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Investigation the role of hippo signaling in metformin-induced apoptosis and autophagy
mechanisms in MDA-MB-231 breast cancer cells

1
Zeynep Gülşah Sonalp , Özge Rencüzoğulları 1
1 Istanbul Kultur University, Science and Literature Faculty, Department of Molecular Biology and Genetics, Atakoy
Campus, 34156 Istanbul/Turkey

Background: Metformin is a biguanide-class antidiabetic drug administered as first-line therapy in patients
with type 2 diabetes. Since it has been shown that metformin was associated with the decreased risk of
developing estrogen receptor-positive breast cancer, the tumor suppressive and anti-proliferative effects
of metformin were investigated in breast cancer. In this study, we aimed to investigate the role of
metformin-induced hippo signaling-regulated apoptosis in MDA-MB-231 breast cancer cells. Material and
methods: MDA-MB-231 breast cancer cells were treated with various concentrations of metformin (1-10
µM). The effect of metformin on cell survival was analyzed by the cell viability and colony formation assays,
DiOC6 and PI fluorescence stainin. The apoptosis, autophagy and hippo signaling-associated signaling
members were analyzed by immunoblotting. Results: Metformin treatment has been shown to suppress
proliferation with a decrease in colony formation. The control of cell proliferation by hippo signaling was
induced by metformin through increasing the rate of p-YAP (S127) which led to prevention of nuclear
translocation of YAP to increase transcription of cell viability-related genes. Moreover, metformin induced
apoptotic cell death due to increase in the expression of apoptotic markers in MDA-MB-231 cells in a dose-
dependent manner. Moreover, the autophagy mechanism was triggered by metformin treatment and
inhibition of autophagy reduced the tumor growth inhibitory effect of metformin in MDA-MB-231 breast
cancer cells Conclusion: Metformin significantly increased the autophagy and apoptosis through induction
of hippo signaling pathway in breast cancer cells. Therefore, regulation of hippo signaling might be potential
therapeutic target in metformin treatment of breast cancer cells.
Keyword: Metformin, breast cancer, apoptosis, autophagy, hippo pathway

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