The Potential Effect of Metformin on Cancer: An Umbrella Review

Yu, Hong; Zhong, Xi; Gao, Peng; Shi, Jinxin; Wu, Zhonghua; Guo, Zhexu; Wang, Zhenning; Song, Yongxi

doi:10.3389/fendo.2019.00617

Cited by 102 publications

(92 citation statements)

References 63 publications

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“…It has been reported that diabetic patients with metformin treatment had a low incidence of cancer . There exists a close correlation among metformin treatment and cancer incidence or patient survival . For the molecular mechanism of metformin in cancer treatment, it has been reported to inactivate STAT3 or NF‐κB, preventing IL‐6‐induced breast cancer progression .…”

Section: Discussionmentioning

confidence: 99%

“…3 There exists a close correlation among metformin treatment and cancer incidence or patient survival. [4][5][6] For the molecular mechanism of metformin in cancer treatment, it has been reported to inactivate STAT3 or NF-κB, preventing IL-6-induced breast cancer progression. 7 In prostate cancer, lung cancer, colon cancer or breast cancer patients with T2DM, metformin has been shown to reduce the development of tumor and prolong the survival.…”

Section: Discussionmentioning

confidence: 99%

“…A previous investigation revealed a low incidence of cancer in diabetic patients treated with metformin . An increasing number of studies display the relationship among metformin treatment and cancer incidence or patient survival . Metformin is able to inactivate STAT3 and NF‐κB to suppress IL‐6‐induced breast cancer progression .…”

Section: Introductionmentioning

confidence: 99%

“…3 An increasing number of studies display the relationship among metformin treatment and cancer incidence or patient survival. [4][5][6] Metformin is able to inactivate STAT3 and NF-κB to suppress IL-6-induced breast cancer progression. 7 Some researchers have observed that metformin can reduce the development of tumor and prolong the survival of patients with T2DM and different cancers, such as prostate cancer, lung cancer, colon cancer or breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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Metformin alleviates breast cancer through targeting high‐mobility group AT‐hook 2

Wang

Ren

et al. 2020

Thoracic Cancer

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Background As a classic oral drug used in diabetic patients, metformin has exhibited an anticancer role in many types of cancers in recent years. Here, we aimed to investigate the role of metformin in the growth of breast cancer and its novel targets. Methods A cell viability assay was utilized to examine the inhibitory effect of metformin on proliferation of breast cancer cells. Western blotting and RT‐PCR assays were used to detect the regulation of metformin on the expression of oncogenic HMGA2. The luciferase reporter vector of HMGA2 promoter was constructed. A luciferase reporter gene assay was performed to analyze the effect of metformin on HMGA2 promoter activity in breast cancer cells. Chromatin immunoprecipitation (ChIP) assay was performed to show the binding of Sp1 to HMGA2 promoter in breast cancer cells with or without metformin treatment. The function of metformin‐regulated HMGA2 in breast cancer growth was tested using a cell viability assay. Results Cell proliferation was obviously inhibited in breast cancer cells treated with different concentrations of metformin. The level of mRNA and protein of HMGA2 was significantly reduced by metformin in the cells. Mechanistically, metformin was able to inactivate the HMGA2 promoter through downregulating transcription factor Sp1 in the cells. In terms of function, treatment with metformin suppressed the proliferation of breast cancer cells and overexpressed HMGA2 reversed the inhibition of cell proliferation mediated by metformin. Conclusion Metformin resists the growth of breast cancer through targeting Sp1/HMGA2 signal.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metformin alleviates breast cancer through targeting high‐mobility group AT‐hook 2

Wang

Ren

et al. 2020

Thoracic Cancer

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“…Several studies suggested the anticancer property of drug 24. The drug 24 at the dose of 250-500 mg/day has been shown to reduce the risk of cancer as well as its daily dose reduces the incidence of gastrological cancer in patients with diabetes [59,60].…”

Section: Introductionmentioning

confidence: 99%

A medicinal chemistry perspective of drug repositioning: Recent advances and challenges in drug discovery

Pillaiyar

Meenakshisundaram²,

Manickam

et al. 2020

European Journal of Medicinal Chemistry

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Drug repurposing is a strategy consisting of finding new indications for already known marketed drugs used in various clinical settings or highly characterized compounds despite they can be failed drugs. Recently, it emerges as an alternative approach for the rapid identification and development of new pharmaceuticals for various rare and complex diseases for which lack the effective drug treatments. The success rate of drugs repurposing approach accounts for approximately 30% of new FDA approved drugs and vaccines in recent years.This review focuses on the status of drugs repurposing approach for various diseases including skin diseases, infective, inflammatory, cancer, and neurodegenerative diseases.Efforts have been made to provide structural features and mode of actions of drugs.Keywords: Cancer, drug repositioning, drug reprofiling, recycling of drugs, drug discovery, inflammation, neurodegenerative diseases, skin diseases. since clinical and pre-clinical studies of the re-purposed candidates are already being documented in the original indication(s). Thus, it reduces the time and cost needed to reach the market and risk intrinsic to any research and development program. Moreover, the risk of clinical failure is also low. As an added advantage, this approach gives a possibility to widen the market and to prolong the application of the patent life of a drug. There are mainly two ways to proceed drug-repositioning approach such as experimental strategies and computational strategies.Experimental repurposing strategies include binding assays and phenotypic screening methods, which can be to find binding interactions of drug molecules to assay components and to identify lead compounds from a vide range of compound libraries, respectively [10].Computational approaches are categorized into target-/mechanism based, knowledge-based, pathway-and network-based approaches. These approaches are proven economic in discovering novel therapeutic ligands. Most notably, computational methods augment the drug discovery process by effectively utilizing cheminformatics, bioinformatics, network biology and systems biology. More specifically, these methods exploit known targets, drugs, disease biomarkers or pathways to establish novel methods and accelerate the planning of crucial clinical trials [11].In this perspective, we focused on the status of drugs repurposing approaches for various diseases including skin diseases, infective, inflammatory, cancer, and neurodegenerative diseases. Efforts have been made to provide structural features, and modes of action of drugs, which are exclusively small molecules, peptidomimetics, and macrocyclic compounds.Antibodies, vaccines, and any other biological drugs are not discussed. Drugs repositioning for skin whitening activity.Melanin is a collection of natural pigments that primarily determine the skin, hair and hair color of the human. Melanocytes, which are found in the basal layer of the epidermis, produce melanin by the process called melanogenesis upon the skin exposure to the ultra...

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Effects of metformin on cancers in experimental and clinical studies: Focusing on autophagy and AMPK/mTOR signaling pathways

Zamanian,

Golmohammadi,

Yumashev

et al. 2024

Cell Biochemistry & Function

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Metformin (MET) is a preferred drug for the treatment of type 2 diabetes mellitus. Recent studies show that apart from its blood glucose‐lowering effects, it also inhibits the development of various tumours, by inducing autophagy. Various studies have confirmed the inhibitory effects of MET on cancer cell lines’ propagation, migration, and invasion. The objective of the study was to comprehensively review the potential of MET as an anticancer agent, particularly focusing on its ability to induce autophagy and inhibit the development and progression of various tumors. The study aimed to explore the inhibitory effects of MET on cancer cell proliferation, migration, and invasion, and its impact on key signaling pathways such as adenosine monophosphate‐activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and PI3K. This review noted that MET exerts its anticancer effects by regulating key signalling pathways such as phosphoinositide 3‐kinase (PI3K), LC3‐I and LC3‐II, Beclin‐1, p53, and the autophagy‐related gene (ATG), inhibiting the mTOR protein, downregulating the expression of p62/SQSTM1, and blockage of the cell cycle at the G0/G1. Moreover, MET can stimulate autophagy through pathways associated with the 5′ AMPK, thereby inhibiting he development and progression of various human cancers, including hepatocellular carcinoma, prostate cancer, pancreatic cancer, osteosarcoma, myeloma, and non‐small cell lung cancer. In summary, this detailed review provides a framework for further investigations that may appraise the autophagy‐induced anticancer potential of MET and its repurposing for cancer treatment.

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The Potential Effect of Metformin on Cancer: An Umbrella Review

Cited by 102 publications

References 63 publications

Metformin alleviates breast cancer through targeting high‐mobility group AT‐hook 2

Metformin alleviates breast cancer through targeting high‐mobility group AT‐hook 2

A medicinal chemistry perspective of drug repositioning: Recent advances and challenges in drug discovery

Effects of metformin on cancers in experimental and clinical studies: Focusing on autophagy and AMPK/mTOR signaling pathways

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