Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

Biochemical and Biophysical Research Communications
Lei HuaiJianxiang Wang

Abstract

Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RARα and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

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Citations

Mar 19, 2013·European Journal of Pharmacology·Christos V Rizos, Moses S Elisaf
Oct 17, 2013·Carcinogenesis·Tunde AkinyekeXin Li
Apr 8, 2015·Experimental Hematology·Ichiro KawashimaKeita Kirito
Jan 28, 2014·Cancer Letters·Célia RosilioJean-François Peyron
Apr 23, 2016·The International Journal of Biochemistry & Cell Biology·Chunyang DaiXiaoling Ma
Jan 19, 2018·Current Medicinal Chemistry·Dora VisnjicHrvoje Lalic
Aug 16, 2018·Frontiers in Physiology·Min LiYan Lu
Aug 28, 2018·Frontiers in Endocrinology·Giulia Biondani, Jean-François Peyron
Mar 23, 2021·Oncology Reviews·Monika Podhorecka

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