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Arch Oral Biol. 2020 Mar 19;113:104710. doi: 10.1016/j.archoralbio.2020.104710. [Epub ahead of print]

Metformin treatment decreases the expression of cancer stem cell marker CD44 and stemness related gene expression in primary oral cancer cells.

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Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia. Electronic address:



Metformin, a common drug for diabetes treatment has shown promising characteristics against wide types of cancer cells in vitro as well as in vivo in the context of halted growth of cancer. But, it was unclear whether cancer stem cells are affected by the metformin treatment. Here, we attempt to find out the effect of metformin on cancer stem cell marker CD44 and stemness related transcription factors including OCT4, SOX2, NANOG, c-Myc and KLF4.


We prepared single-cell suspension from primary oral tumors and subjected the cells to grow in vitro. Gene expression of transcription factors was assessed by real-time PCR. Further, the expression of CD44 was checked by flow Cytometry.


Metformin showed downregulation in the gene expressions of stemness related transcription factors OCT4, SOX2, NANOG, c-Myc, and KLF4 in a dose-dependent as well as time-dependent manner. Also, the most effective concentration of metformin at 25 μM was found to decrease the expression of CD44 in the primary tumor cells in a time-dependent manner.


Continuous treatment of lower concentrations of metformin decreases the expression of cancer stem cell markers at the transcription level and cancer stem cell-surface marker CD44 in primary oral cancer cells.


CD44; Cancer stem cell; Metformin; OSCC; Stemness genes

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