ArticlePloS one2014
Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 49 citations in OpenAlex.
- Additive Anticancer and Antioxidant Effects of Metformin and Luteolin in Breast and Colorectal Cancer Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The development and benefits of metformin in various diseases.Frontiers of medicine · 2023Review
- The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment.Frontiers in immunology · 2023Review
- Phosphoproteomics Reveals the AMPK Substrate Network in Response to DNA Damage and Histone Acetylation.Genomics, proteomics & bioinformatics · 2022Article
- Repositioning metformin and propranolol for colorectal and triple negative breast cancers treatment.Scientific reports · 2021Article
- Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects.Journal of experimental & clinical cancer research : CR · 2019Review
- The AMPK-activator AICAR in thyroid cancer: effects on CXCL8 secretion and on CXCL8-induced neoplastic cell migration.Journal of endocrinological investigation · 2018Article
- Metformin and blood cancers.Clinics (Sao Paulo, Brazil) · 2018Review
- Molecular Characterization of Colorectal Signet-Ring Cell Carcinoma Using Whole-Exome and RNA Sequencing.Translational oncology · 2018Article
- Therapeutic strategies against cancer stem cells in human colorectal cancer.Oncology letters · 2017Article
- Effect of AICAR and 5-Fluorouracil on X-ray Repair, Cross-Complementing Group 1 Expression, and Consequent Cytotoxicity Regulation in Human HCT-116 Colorectal Cancer Cells.International journal of molecular sciences · 2017Article
- Aging, Metabolism, and Cancer Development: from Peto's Paradox to the Warburg Effect.Aging and disease · 2017Review
- Colon cancer modulation by a diabetic environment: A single institutional experience.PloS one · 2017Article
- Functional characterization of AMP-activated protein kinase signaling in tumorigenesis.Biochimica et biophysica acta · 2016Review
- Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-κB/HIF-1α signal axis.Scientific reports · 2016Article
- NT1014, a novel biguanide, inhibits ovarian cancer growth in vitro and in vivo.Journal of hematology & oncology · 2016Article
- Metformin and AICAR regulate NANOG expression via the JNK pathway in HepG2 cells independently of AMPK.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Review
- Metformin and soybean-derived bioactive molecules attenuate the expansion of stem cell-like epithelial subpopulation and confer apoptotic sensitivity in human colon cancer cells.Genes & nutrition · 2015Article
- Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) is still the third most common cancer and the second most common causes of cancer-related death around the world. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been shown to have a suppressive effect on CRC risk and mortality, but not all laboratory studies suggest that metformin has antineoplastic activity. Here, we investigated the effect of metformin and AMPK activator AICAR on CRC cells proliferation. As a result, metformin did not inhibit cell proliferation or induce apoptosis for CRC cell lines in vitro and in vivo. Different from metformin, AICAR emerged antitumor activity and sensitized anticancer effect of 5-FU on CRC cells in vitro and in vivo. In further analysis, we show that AMPK activation may be a key molecular mechanism for the additive effect of AICAR. Taken together, our results suggest that metformin has not antineoplastic activity for CRC cells as a single agent but AMPK activator AICAR can induce apoptosis and enhance the cytotoxic effect of 5-FU through AMPK activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.