ArticleCancer science2019
Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Effects of Glutamine or Glucose Deprivation on Inflammation and Tight Junction Disruption in Yak Rumen Epithelial Cells.Animals : an open access journal from MDPI · 2024Article
- Pharmacological characterization of the antidiabetic drug metformin in atherosclerosis inhibition: A comprehensive insight.Immunity, inflammation and disease · 2024Review
- Mitochondrial Elongation and ROS-Mediated Apoptosis in Prostate Cancer Cells under Therapy with Apalutamide and Complex I Inhibitor.International journal of molecular sciences · 2024Article
- Metformin role in Parkinson's disease: a double-sword effect.Molecular and cellular biochemistry · 2024Review
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- Oleic acid from cancer-associated fibroblast promotes cancer cell stemness by stearoyl-CoA desaturase under glucose-deficient condition.Cancer cell international · 2022Article
- Targeting USP9X-AMPK Axis in ARID1A-Deficient Hepatocellular Carcinoma.Cellular and molecular gastroenterology and hepatology · 2022Article
- Effects of different doses of metformin on bone mineral density and bone metabolism in elderly male patients with type 2 diabetes mellitus.World journal of clinical cases · 2020Article
- Physiological expression and function of the MDR1 transporter in cytotoxic T lymphocytes.The Journal of experimental medicine · 2020Article
- Whole-blood transcriptome profiling reveals signatures of metformin and its therapeutic response.PloS one · 2020Article
- Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1.Cancer science · 2019Article
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Authors and funding
6 authors at 1 institution in 3 countries.
Funding
Abstract
Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose-starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m-chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.
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