Metformin combined with glucose starvation synergistically suppress triple-negative breast cancer by enhanced unfolded protein response

Lü, Ying; Zhang, Qingqian; Yang, Jun; He, Wei; Jiang, Yulan; Yu, Chunhua; Wang, Yifan

doi:10.1016/j.bbrc.2023.07.029

Cited by 5 publications

(2 citation statements)

References 41 publications

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“…This data suggests that glucose deprivation makes cells more sensitive to metformin inhibition of the mTOR pathway. Furthermore, in MDA-MB-231 cells, metformin treatment combined with glucose deprivation has been shown to activate genes related to the unfolded protein response of the endoplasmic reticulum, decrease proliferation, and increase cell apoptosis [ 41 ].…”

Section: Preclinical Evidence: Findings From In Vitro and In Vivo Modelsmentioning

confidence: 99%

“…We also propose that future preclinical and clinical studies should consider the effect of diet and dietary components on the efficacy of metformin treatment. Current data demonstrate that glucose levels likely modulate the efficacy of metformin in preclinical models, and that strategies such as caloric restriction, short-term starvation, and ketogenic diets enhance the benefits of metformin for improving tumor outcomes [ 41 , 42 , 43 ]. Another study has shown that metformin was more effective at reducing tumor volume in rodents when combined with a diet depleted of the amino acid asparagine [ 158 ].…”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

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Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies

Corleto,

Strandmo,

Giles

2024

Pharmaceuticals

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Over the last several decades, a growing body of research has investigated the potential to repurpose the anti-diabetic drug metformin for breast cancer prevention and/or treatment. Observational studies in the early 2000s demonstrated that patients with diabetes taking metformin had decreased cancer risk, providing the first evidence supporting the potential role of metformin as an anti-cancer agent. Despite substantial efforts, two decades later, the exact mechanisms and clinical efficacy of metformin for breast cancer remain ambiguous. Here, we have summarized key findings from studies examining the effect of metformin on breast cancer across the translational spectrum including in vitro, in vivo, and human studies. Importantly, we discuss critical factors that may help explain the significant heterogeneity in study outcomes, highlighting how metformin dose, underlying metabolic health, menopausal status, tumor subtype, membrane transporter expression, diet, and other factors may play a role in modulating metformin’s anti-cancer effects. We hope that these insights will help with interpreting data from completed studies, improve the design of future studies, and aid in the identification of patient subsets with breast cancer or at high risk for the disease who are most likely to benefit from metformin treatment.

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Section: Preclinical Evidence: Findings From In Vitro and In Vivo Modelsmentioning

confidence: 99%

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies

Corleto,

Strandmo,

Giles

2024

Pharmaceuticals

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Metformin: From diabetes to cancer to prolongation of life

Sirtori,

Castiglione,

Pavanello

2024

Pharmacological Research

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Metformin (The Miracle Drug) Kinetics in Different Diseases such as Cancer

Tolou-Ghamari

2024

CCTR

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Metformin, a miracle drug that was introduced a century ago, could be considered for various aspects of diseases such as diabetes (type 1 and 2), cancer prevention or chemotherapy, and metabolic and neurodegenerative disease. It is well known that the frequency of cancer is higher in patients with type 2 diabetes mellitus. This review aims to provide updated information regarding clinical pharmacokinetics and the mechanism of action of Metformin in different diseases such as cancer. Diabetes type 1 is another chronic autoimmune disease detected usually in early childhood due to immune-mediated devastation of insulin-producing pancreatic beta-cells. Because of the lack of effective therapeutic approaches, its prevalence is increasing. Regarding cancer, an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths were reported in 2020 worldwide. By 50-60% bioavailability, the main route of metformin excretion is through urine. Its mechanism of action is based on 1) initiation of adenosine monophosphate-activated kinase, 2) block proinflammatory paths in perivascular adipose tissue, 3) decrease in monocyte-to-macrophage differentiation in vascular tissues, and 4) improvement in endothelial function. Metformin induces adenosine monophosphate-activated protein kinase signaling and suppresses gluconeogenesis. Antitumor properties of Metformin include a decrease in reactive oxygen species generation and inducing autophagy. In addition to glucose-lowering effects, Metformin has moderate anti-inflammatory and antioxidative effects. It could improve lipid profile and reduce overweight individuals' body mass and arterial blood pressure. In type 1 diabetes, Metformin reduces the requirement for daily insulin and improves glycemia. Its long-term use decreases cardiovascular events. In addition to inhibiting the synthesis of lipids via a reduction in oxidative stress, Metformin inhibits inflammation and increases energy metabolism. Finally, by reducing micro- and macro-vascular consequences, mortality-related diabetes and cancer decline by metformin administration. Therefore, in addition to diabetes, Metformin could reduce the proliferation of cancer cells and the possibility of malignancies in different types of cancer.

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Metformin combined with glucose starvation synergistically suppress triple-negative breast cancer by enhanced unfolded protein response

Cited by 5 publications

References 41 publications

Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies

Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies

Metformin: From diabetes to cancer to prolongation of life

Metformin (The Miracle Drug) Kinetics in Different Diseases such as Cancer

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