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Effect of Metformin on P53 and its Interacting Partners in Breast Cancer Cell Line MCF-7

Effect of Metformin on P53 and its Interacting Partners in Breast Cancer Cell Line MCF-7

Mehroze Amin1, Afifa Yaqub1, Qindeel Fatima1, Rabail Hassan Toor1,3 and Abdul Rauf Shakoori1,2*

1School of Biological Sciences, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, Pakistan
2Cancer Research Centre, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, Pakistan
3UVM Cancer Center, Larner College of Medicine, Department of Biochemistry, University of Vermont, Burlington, VT 05405, USA
 
* Corresponding author: arshakoori.sbs@pu.edu.pk, arshaksbs@yahoo.com

ABSTRACT

Metformin is known to favor p53 anti-cancer activity and promote apoptosis and cell senescence in cancer cells. It is also known to decrease the incidence of several cancers though it is not entirely true for breast cancer. In the present study, the effect of metformin has been studied on the expression of p53 and its interacting partners MDM-2, PIRH2 and ΔNp73 in breast cancer cell line MCF-7 and non-cancerous kidney cell line HEK2093. Analysis of the cytotoxicity and proliferation parameters showed that higher concentrations of metformin were cytotoxic for the breast cancer cells with EC50 of 22.75µM. Analysis of expression of p53 and the interacting partner genes showed that metformin upregulated p53 expression in a dose-dependent manner, while the expression of interacting partners is downregulated indicating that metformin exhibits the anti-cancerous effect by regulating the p53 pathway. Altogether this study reports the effect of metformin on the expression of p53 and its interacting partners MDM2, PIRH2 and ΔNp73in breast cancer cell line MCF-7, thereby providing evidence that metformin modulates p53 pathway to exhibit its anti-cancer property. Hence , metformin can be a potential therapeutic candidate for breast cancer treatment. However, further investigations are required to provide insight into the therapeutic potential od metformin for cancer.

 

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Pakistan Journal of Zoology

October

Vol. 54, Iss. 5, Pages 2003-2500

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