Metformin downregulates the mitochondrial carrier SLC25A10 in a glucose dependent manner

Biochemical Pharmacology
Qian ZhaoAnna Karlsson

Abstract

Metformin, a commonly used agent in the treatment of type 2 diabetes, is also associated with reduced risk of cancer development and improvement in cancer survival. Although much is known about metformin, the mechanisms behind its anti-cancer properties are not fully understood. In this study we addressed the role of a mitochondrial transporter commonly upregulated in cancer cells, SLC25A10, for cell survival and metabolism in the presence of metformin. SLC25A10 is a carrier in the mitochondrial inner membrane that transports malate and succinate out of the mitochondria, in exchange of phosphate and sulfate. We show that metformin treatment results in decreased gene expression of the SLC25A10 carrier both in lung cancer A549 mock cells and A549 SLC25A10 knockdown (siSLC25A10) cells. The decrease was even more pronounced when cells were grown at low glucose concentrations. The expression levels of key enzymes in glucose metabolism showed slightly altered mean values for all genes tested in both control cells and siSLC25A10 cells upon metformin treatment. The gene expression of the metabolic regulator glutamic-oxaloacetic transaminase 1 decreased in wild type cells upon metformin treatment whereas there was a trend of increased e...Continue Reading

Citations

Jun 5, 2020·Journal of Receptor and Signal Transduction Research·Zengjun XieLiang Zhao
Apr 7, 2020·Journal of Receptor and Signal Transduction Research·Wenjun LiangMingxia Yang
May 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Luc RochetteCatherine Vergely

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