Metformin decreases lung cancer risk in diabetic patients in a dose-dependent manner

Tsai, Ming‐Ju; Yang, Chih‐Jen; Kung, Ya-Ting; Sheu, Chau‐Chyun; Shen, Yu‐Ting; Chang, Pi-Yu; Huang, Ming‐Shyan; Chiu, Herng‐Chia

doi:10.1016/j.lungcan.2014.09.012

Cited by 46 publications

(56 citation statements)

References 37 publications

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“…We first conducted CCK-8 cell proliferation assay in osteosarcoma MG63 cells treated with metformin. In consistence with a previous report, metformin could inhibit cell growth in a dose-and time-dependent manner [20]. In addition, we obtained IC 50 value (15 mM) at 48 h, which was comparatively lower than in a previous study (20 mM), to test signaling pathway by Western blot.…”

Section: Discussionsupporting

confidence: 86%

“…c MMP2, MMP9, and β-actin (loading control) expressions were measured by Western blot (* and ** compared with the CON group. **p<0.01, *p<0.05) (metformin 0 mM) and metformin at different concentrations (5,10,15,20,25, and 30 mM) and were continuously incubated for 24, 48, and 72 h. Subsequently, 10 μl CCK-8 solution was added to each well. Then, cells were incubated at 37°C for 3 h and the absorbance (A450) was finally read at 450 nm using a microplate reader.…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

“…To observe the effect of metformin on the proliferation in OS cells in vitro, MG63 cells were treated with control (metformin 0 mM) and metformin at a variety of concentrations (1,5,10,15,20,25, and 30 mM) for 24, 48, and 72 h, respectively. Treatment with metformin could inhibit the growth of MG63 cells, and the inhibitory effects were in a dose-and timedependent manner with an IC 50 of 15 mM after exposure for Fig.…”

Section: The Effects Of Metformin On Cell Growth Apoptosis and Cellmentioning

confidence: 99%

“…Recent evidence indicate that metformin may reduce the risk of cancer in patients with type 2 diabetes [19][20][21]. Furthermore, in vivo and in vitro studies have demonstrated that metformin inhibits tumor cells and tumor stem cell growth and survival in numerous tumors [22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

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Metformin inhibits the proliferation, metastasis, and cancer stem-like sphere formation in osteosarcoma MG63 cells in vitro

Zhang

et al. 2015

Tumor Biol.

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Metformin is an oral drug that has been widely used to treat type 2 diabetes mellitus. Interestingly, accumulated evidence indicate that metformin may reduce the risk of cancer in patients with type 2 diabetes and inhibit tumor cell growth and survival in numerous malignancies, including osteosarcoma (OS) cells. In the present study, we aimed to investigate the effects of metformin on the proliferation, migration, invasion, and sphere formation in OS MG63 cells in vitro. Metformin suppressed OS MG63 cell proliferation in a dose- and time-dependent manner and markedly blocked anti-metastatic potentials, migration, and invasion, by downregulating matrix metalloproteinase 2 (MMP2) and MMP9. Besides, we established OS cancer stem-like cell (CSC) model with sarcosphere formation assay and demonstrated that metformin posed damage on CSCs in OS by inhibiting sphere formation and by inducing their stemness loss. The stemness of CSCs in OS such as self-renewal and differentiation potentials was both impaired with a significant decrease of Oct-4 and Nanog activation. Consistent with this, the positive rates of CD90, CD133, and stage-specific embryonic antigen-4 (SSEA-4) were all observed with reductions in response to metformin exposure. In addition, Western blot showed that metformin activated AMPKα at Tyr172, followed by a downregulated phosphorylation of mammalian target of rapamycin (mTOR)/S6 and feedback activation of p-AKT Ser(473) in both OS MG63 cells and CSCs. This indicates that AMPK/mTOR/S6 signaling pathway might be involved in the growth inhibition of both OS MG63 cells and CSCs. These results suggest that metformin, a potential anti-neoplastic agent, might make it a novel therapeutic choice for the treatment of OS in the future.

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Section: Discussionsupporting

confidence: 86%

Section: Cell Proliferation Assaymentioning

confidence: 99%

Section: The Effects Of Metformin On Cell Growth Apoptosis and Cellmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metformin inhibits the proliferation, metastasis, and cancer stem-like sphere formation in osteosarcoma MG63 cells in vitro

Zhang

et al. 2015

Tumor Biol.

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“…They observed that metformin would reduce the risk of cancer in Type 2 diabetes mellitus patient in dose dependent manner in a study on Chinese population. They mentioned that the chemo-preventive effect of metformin deserves further study [8].…”

Section: Statisticsmentioning

confidence: 99%

Recent Developments in Cancer

Remella¹

2015

J Dev Drugs

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Cancer is one among the leading cause of deaths worldwide. In the present review I have mentioned recent statistics of cancer and mentioned few recent developments in cancer research especially on the most common cancers like lung cancer, breast cancer, prostate cancer, skin cancer and endometrial cancer which would give a brief idea on the ongoing research in cancer for the students, Research Scholars.

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Metformin blocks MYC protein synthesis in colorectal cancer via mTOR‐4EBP‐eIF4E and MNK1‐eIF4G‐eIF4E signaling

et al. 2018

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The antidiabetic drug metformin has been associated with reduced colorectal cancer (CRC) risk and improved prognosis of CRC patients. However, the detailed mechanisms underlying such beneficial effects remain unknown. In this study, we aimed to evaluate metformin activity in CRC models and unveil the underlying molecular mechanisms. We showed that metformin inhibits CRC cell proliferation by arresting cells in the G1 phase of the cell cycle and dramatically reduces colony formation of CRC cells. We discovered that metformin causes a robust reduction of MYC protein level. Through the use of luciferase assay and coincubation with either protein synthesis or proteasome inhibitors, we demonstrated that regulation of MYC by metformin is independent of the proteasome and 3′ UTR‐mediated regulation, but depends on protein synthesis. Data from polysome profiling and ribopuromycylation assays showed that metformin induced widespread inhibition of protein synthesis. Repression of protein synthesis by metformin preferentially affects cell cycle‐associated proteins, by altering signaling through the mTOR‐4EBP‐eIF4E and MNK1‐eIF4G‐eIF4E axes. The inhibition of MYC protein synthesis may underlie metformin's beneficial effects on CRC risk and prognosis.

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Metformin decreases lung cancer risk in diabetic patients in a dose-dependent manner

Cited by 46 publications

References 37 publications

Metformin inhibits the proliferation, metastasis, and cancer stem-like sphere formation in osteosarcoma MG63 cells in vitro

Metformin inhibits the proliferation, metastasis, and cancer stem-like sphere formation in osteosarcoma MG63 cells in vitro

Recent Developments in Cancer

Metformin blocks MYC protein synthesis in colorectal cancer via mTOR‐4EBP‐eIF4E and MNK1‐eIF4G‐eIF4E signaling

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