The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK
Open accessAbstract
BACKGROUND: We examined the potential of metformin (MET) to enhance non-small cell lung cancer (NSCLC) responses to ionising radiation (IR). METHODS: Human NSCLC cells, mouse embryonic fibroblasts from wild-type and AMP-activated kinase (AMPK) α1/2-subunit(-/-) embryos (AMPKα1/2(-/-)-MEFs) and NSCLC tumours grafted into Balb/c-nude mice were treated with IR and MET and subjected to proliferation, clonogenic, immunoblotting, cell cycle and apoptosis assays and immunohistochemistry (IHC). RESULTS: Metformin (2.5 μM-5 mM) inhibited proliferation and radio-sensitised NSCLC cells. Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis. ATM inhibition blocked MET and IR activation of AMPK. Non-small cell lung cancer cells with inhibited AMPK and AMPKα1/2(-/-)-MEFs were resistant to the antiproliferative effects of MET and IR. Metformin or IR inhibited xenograft growth and combined treatment enhanced it further than each treatment alone. Ionising radiation and MET induced (i) sustained activation of ATM-AMPK-p53/p21(cip1) and inhibition of Akt-mTOR-4EBP1 pathways in tumours, (ii) reduced expression of angiogenesis and (iii) enhanced expression of apoptosis markers. CONCLUSION: Clinically achievable MET doses inhibit NSCLC cell and tumour growth and sensitise them to IR. Metformin and IR mediate their action through an ATM-AMPK-dependent pathway. Our results suggest that MET can be a clinically useful adjunct to radiotherapy in NSCLC.
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AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
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The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
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The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
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“Retrospective analysis suggested that MET may enhance chemotherapy responses in women with breast cancer (Jiralerspong et al, 2009).”
BackgroundSahra, I. B., Laurent, K., Loubat, A., Giorgetti-Peraldi, S., Colosetti, P., Auberger, P., Tanti, J. F., Le Marchand-Brustel, Y., & Bost, F. (2008) · Oncogene · doi:10.1038/sj.onc.1211024 · Cited by 861
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Use of Metformin in the Setting of Mild-to-Moderate Renal Insufficiency
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“AMP-activated kinase is suggested to participate in angiogenesis (Nagata et al, 2003) and MET was suggested to normalise tumour vasculature in breast cancer and inhibit angiogenesis in ovarian cancer xenografts (Rattan et al, 2011).”
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Weinberg, S. E., & Chandel, N. S. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1712 · Cited by 1,381
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Barron, C. C., Bilan, P. J., Tsakiridis, T., & Tsiani, E. (2016) · Metabolism · doi:10.1016/j.metabol.2015.10.007 · Cited by 435
Self-citationAnticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols
Moore, J., Yousef, M., & Tsiani, E. (2016) · Nutrients · doi:10.3390/nu8110731 · Cited by 292
Self-citationSanli, T., Steinberg, G. R., Singh, G., & Tsakiridis, T. (2014) · Cancer Biology & Therapy · doi:10.4161/cbt.26726 · Cited by 220
Self-citationArrieta, O., Barrón, F., Padilla, M.-Á. S., Avilés-Salas, A., Ramírez-Tirado, L. A., Arguelles Jiménez, M. J., Vergara, E., Zatarain-Barrón, Z. L., Hernández-Pedro, N., Cardona, A. F., et al. (2019) · JAMA Oncology · doi:10.1001/jamaoncol.2019.2553 · Cited by 179
Metadata
- Authors
- Storozhuk, Y., Hopmans, S. N., Sanli, T., Barron, C., Tsiani, E., Cutz, J.-C., Pond, G., Wright, J., Singh, G., & Tsakiridis, T.
- Venue
- British Journal of Cancer
- Published
- 2013-04-30
- Volume
- 108
- Issue
- 10
- Pages
- 2021-2032
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- OpenAlex
- W2076908467
- Cited by
- 273
- References
- 13
- FWCI
- 12.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Storozhuk, Y., Hopmans, S. N., Sanli, T., Barron, C., Tsiani, E., Cutz, J.-C., Pond, G., Wright, J., Singh, G., & Tsakiridis, T. (2013). Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. British Journal of Cancer. https://doi.org/10.1038/bjc.2013.187
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