Metformin Reduces Thyroid Cancer Tumor Growth in the Metastatic Niche of Bone by Inhibiting Osteoblastic RANKL Productions

Shin, Hyun Soo; Sun, Hyun Jin; Whang, Young Mi; Park, Young Joo; Park, Do Joon; Cho, Sun Wook

doi:10.1089/thy.2019.0851

Cited by 14 publications

(14 citation statements)

References 49 publications

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“…AMPK-Gfi1-OPN axis also play important role in bone and glucose metabolism [49]. Mai et al found that metformin stimulates OPN and reduces RANKL expression in osteoblasts and ovariectomized rats [50][51][52]. OPN mediated AMPK regulation of osteogenesis and inhibited adipogenesis [49].…”

Section: Discussionmentioning

confidence: 99%

The effects of metformin and alendronate in attenuating bone loss and improving glucose metabolism in diabetes mellitus mice

Zhou

Guan

Liu

et al. 2022

Aging

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Background: To explore the anti-osteoporosis and anti-diabetes effects and potential underlying mechanisms of treatment with metformin and alendronate in diabetes mellitus mice. Methods: Eight-week-old C57 BL/KS db/db and db/+ female mice were evaluated according to the following treatment group for 12 weeks: control group, diabetes mellitus group, diabetes mellitus with metformin group, diabetes mellitus with Alendronate group, diabetes mellitus with metformin plus alendronate group. Glucose level, glucose tolerance test, bone mineral density, bone microarchitecture, bone histomorphometry, serum biomarkers, and qPCR analysis. Results: Combined metformin and alendronate can improve progression in glucose metabolism and bone metabolism, including blood glucose levels, blood glucose levels after 4 and 16 hours fasting, glucose tolerance test results, insulin sensitivity and reduces bone loss than the diabetes group. The use of alendronate alone can increase significantly serum glucagon-like peptide-1 levels than the diabetes group. The use of metformin alone can improve bone microstructure such as Tb.Sp and Tb.N of spine in diabetic mice. Conclusion: The combined use of alendronate and metformin has an anti-diabetes and anti-osteoporotic effect compared with diabetic mice, but they appear to act no obvious synergistically between alendronate and metformin.

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Section: Discussionmentioning

confidence: 99%

The effects of metformin and alendronate in attenuating bone loss and improving glucose metabolism in diabetes mellitus mice

Zhou

Guan

Liu

et al. 2022

Aging

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“…The increase in AMPK activity induced by metformin appears to induce the G1 phase of the cell cycle, which leads to the arrest of cell proliferation without activating the apoptotic mechanism [ 42 ]. Moreover, through AMPK activation, metformin indirectly reduces cancer cell viability by inducing apoptosis and inhibits osteoclast differentiation in bone tumors [ 106 , 107 ]. Furthermore, the reduction in blood glucose and insulin levels may impair the cancer’s growth by AMPK activation, which leads to decreased transcription of gluconeogenic genes by inhibition of histone deacetylases (HDAC) and decreased lipogenic gene expression by inhibition of sterol regulatory element binding proteins [ 108 ].…”

Section: Anti-cancer Effectmentioning

confidence: 99%

Metformin Intervention—A Panacea for Cancer Treatment?

Buczyńska

Sidorkiewicz

Krętowski

et al. 2022

Cancers

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The molecular mechanism of action and the individual influence of various metabolic pathways related to metformin intervention are under current investigation. The available data suggest that metformin provides many advantages, exhibiting anti-inflammatory, anti-cancer, hepatoprotective, cardioprotective, otoprotective, radioprotective, and radio-sensitizing properties depending on cellular context. This literature review was undertaken to provide novel evidence concerning metformin intervention, with a particular emphasis on cancer treatment and prevention. Undoubtedly, the pleiotropic actions associated with metformin include inhibiting inflammatory processes, increasing antioxidant capacity, and improving glycemic and lipid metabolism. Consequently, these characteristics make metformin an attractive medicament to translate to human trials, the promising results of which were also summarized in this review.

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“…Similarly, ATC-CM induced osteoclast differentiation of bone-marrow-derived monocyte/macrophage, which was also blocked by metformin treatment. The ATC-CM contained high levels of IL-6/sIL-6R and induced osteoblast RANKL production through gp130/STAT3 signaling; however, this effect was blocked by metformin in a mechanism dependent on AMPK phosphorylation, suggesting that in the tumor microenvironments, p-AMPK inhibits STAT3 phosphorylation [40].…”

Section: Thyroid Cancermentioning

confidence: 99%

Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models

2022

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Metformin is the most used drug for type 2 diabetes (T2DM). Its antitumor activity has been described by clinical studies showing reduced risk of cancer development in T2DM patients, as well as management of T2DM compared with those receiving other glucose-lowering drugs. Metformin has a plethora of molecular actions in cancer cells. This review focused on in vitro data on the action mechanisms of metformin on thyroid, prostate and head and neck cancer. AMPK activation regulating specific downstream targets is a constant antineoplastic activity in different types of cancer; however, AMPK-independent mechanisms are also relevant. In vitro evidence makes it clear that depending on the type of tumor, metformin has different actions; its effects may be modulated by different cell conditions (for instance, presence of HPV infection), or it may regulate tissue-specific factors, such as the Na+/I− symporter (NIS) and androgen receptors. The hallmarks of cancer are a set of functional features acquired by the cell during malignant development. In vitro studies show that metformin regulates almost all the hallmarks of cancer. Interestingly, metformin is one of these therapeutic agents with the potential to synergize with other chemotherapeutic agents, with low cost, low side effects and high positive consequences. Some questions are still challenging: Are metformin in vitro data able to translate from bench to bedside? Does metformin affect drug resistance? Can metformin be used as a generic anticancer drug for all types of tumors? Which are the specific actions of metformin on the peculiarities of each type of cancer? Several clinical trials are in progress or have been concluded for repurposing metformin as an anticancer drug. The continuous efforts in the field and future in vitro studies will be essential to corroborate clinical trials results and to elucidate the raised questions.

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Metformin Reduces Thyroid Cancer Tumor Growth in the Metastatic Niche of Bone by Inhibiting Osteoblastic RANKL Productions

Cited by 14 publications

References 49 publications

The effects of metformin and alendronate in attenuating bone loss and improving glucose metabolism in diabetes mellitus mice

The effects of metformin and alendronate in attenuating bone loss and improving glucose metabolism in diabetes mellitus mice

Metformin Intervention—A Panacea for Cancer Treatment?

Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models

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