Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
December-2014 Volume 10 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2014 Volume 10 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Effects of metformin on FOXM1 expression and on the biological behavior of acute leukemia cell lines

  • Authors:
    • Bing Zhang
    • Long-Long Liu
    • Xia Mao
    • Dong-Hua Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Hematology, Wuhan General Hospital of Guangzhou Military Command, Wuhan, Hubei 430070, P.R. China
  • Pages: 3193-3198
    |
    Published online on: October 13, 2014
       https://doi.org/10.3892/mmr.2014.2629
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Forkhead box M1 (FOXM1) is a typical proliferation‑associated transcription factor, which is overexpressed in many types of human cancer. We investigated the expression level of FOXM1 in patients with untreated acute leukemia (AL) and explored the correlation between expression levels and AL type. The relationship between the expression of the genes FOXM1 and mammalian target of rapamycin (mTOR) was determined after treatment of ML-2 cells with thiostrepton. The apoptosis, proliferation and cell-cycle progression of ML-2 lines were examined after treatment with metformin. We found that FOXM1 is expressed in the majority of AL patients and that its expression level was associated with the AL type. Thiostrepton is a specific inhibitor of FOXM1, and by inhibiting the FOXM1 expression via thiostrepton, we observed downregulatiion of mTOR; a significant correlation between FOXM1 and mTOR levels was observed. Thus, metformin may be involved in the downregulation of FOXM1. In addition, our study demonstrated that metformin promotes the apoptosis of ML-2 cells, induces cell-cycle arrest at the G0/G1 and G2/M phases, and inhibits proliferation. The potential role of FOXM1 in tumorigenesis renders it an attractive target for anticancer therapy, and metformin may represent a new agent for the treatment of leukemia.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Wang Z, Banerjee S, Kong D, Li Y and Sarkar FH: Down-regulation of Forkhead Box M1 transcription factor leads to the inhibition of invasion and angiogenesis of pancreatic cancer cells. Cancer Res. 67:8293–8300. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Wu QF, Liu C, Tai MH, et al: Knockdown of FoxM1 by siRNA interference decreases cell proliferation, induces cell cycle arrest and inhibits cell invasion in MHCC-97H cells in vitro. Acta Pharmacol Sin. 31:361–366. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Ahmad A, Wang Z, Kong D, et al: FoxM1 down-regulation leads to inhibition of proliferation, migration and invasion of breast cancer cells through the modulation of extra-cellular matrix degrading factors. Breast Cancer Res Treat. 122:337–346. 2010. View Article : Google Scholar

4 

Nakamura S, Hirano I, Okinaka K, et al: The FOXM1 transcriptional factor promotes the proliferation of leukemia cells through modulation of cell cycle progression in acute myeloid leukemia. Carcinogenesis. 31:2012–2021. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH and Huang YC: Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals. BMC Cancer. 11:202011. View Article : Google Scholar

6 

Green AS, Chapuis N, Lacombe C, Mayeux P, Bouscary D and Tamburini J: LKB1/AMPK/mTOR signaling pathway in hematological malignancies: from metabolism to cancer cell biology. Cell Cycle. 10:2115–2120. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Spender LC and Inman GJ: Phosphoinositide 3-kinase/AKT/mTORC1/2 signaling determines sensitivity of Burkitt’s lymphoma cells to BH3 mimetics. Mol Cancer Res. 10:347–359. 2012.PubMed/NCBI

8 

Feng Y, Ke C, Tang Q, et al: Metformin promotes autophagy and apoptosis in esophageal squamous cell carcinoma by downregulating Stat3 signaling. Cell Death Dis. 5:e10882014. View Article : Google Scholar : PubMed/NCBI

9 

Warren M, Luthra R, Yin CC, et al: Clinical impact of change of FLT3 mutation status in acute myeloid leukemia patients. Mod Pathol. 25:1405–1412. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Hegde NS, Sanders DA, Rodriguez R and Balasubramanian S: The transcription factor FOXM1 is a cellular target of the natural product thiostrepton. Nat Chem. 3:725–731. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Wonsey DR and Follettie MT: Loss of the forkhead transcription factor FoxM1 causes centrosome amplification and mitotic catastrophe. Cancer Res. 65:5181–5189. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Bhat UG, Halasi M and Gartel AL: Thiazole antibiotics target FoxM1 and induce apoptosis in human cancer cells. PLoS One. 4:e55922009. View Article : Google Scholar : PubMed/NCBI

13 

Kiyoi H, Yanada M and Ozekia K: Clinical significance of FLT3 in leukemia. Int J Hematol. 82:85–92. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Yanada M, Matsuo K, Suzuki T, Kiyoi H and Naoe T: Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia. 19:1345–1349. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Frohling S, Schlenk RF, Breitruck J, et al: Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood. 100:4372–4380. 2002.

16 

Green AS, Chapuis N, Maciel TT, et al: The LKB1/AMPK signaling pathway has tumor suppressor activity in acute myeloid leukemia through the repression of mTOR-dependent oncogenic mRNA translation. Blood. 116:4262–4273. 2010. View Article : Google Scholar

17 

Memmott RM, Mercado JR, Maier CR, Kawabata S, Fox SD and Dennis PA: Metformin prevents tobacco carcinogen - induced lung tumorigenesis. Cancer Prev Res (Phila). 3:1066–1076. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Oliveras-Ferraros C, Cufi S, Vazquez-Martin A, et al: Micro(mi)RNA expression profile of breast cancer epithelial cells treated with the anti-diabetic drug metformin: induction of the tumor suppressor miRNA let-7a and suppression of the TGFβ-induced oncomiR miRNA-181a. Cell Cycle. 10:1144–1151. 2011.

19 

Hirsch HA, Iliopoulos D, Tsichlis PN and Struhl K: Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 69:7507–7511. 2009. View Article : Google Scholar

20 

Wang X, Hung NJ and Costa RH: Earlier expression of the transcription factor HFH-11B diminishes induction of p21(CIP1/WAF1) levels and accelerates mouse hepatocyte entry into S-phase following carbon tetrachloride liver injury. Hepatology. 33:1404–1414. 2001. View Article : Google Scholar

21 

Wang X, Krupczak-Hollis K, Tan Y, Dennewitz MB, Adami GR and Costa RH: Increased hepatic Forkhead Box M1B (FoxM1B) levels in old-aged mice stimulated liver regeneration through diminished p27Kip1 protein levels and increased Cdc25B expression. J Biol Chem. 277:44310–44316. 2002. View Article : Google Scholar

22 

Sun DF, Zhang YJ, Tian XQ, Chen YX and Fang JY: Inhibition of mTOR signalling potentiates the effects of trichostatin A in human gastric cancer cell lines by promoting histone acetylation. Cell Biol Int. 38:50–63. 2014. View Article : Google Scholar : PubMed/NCBI

23 

MacKenzie MJ, Ernst S, Johnson C and Winquist E: A phase I study of temsirolimus and metformin in advanced solid tumours. Invest New Drugs. 30:647–652. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Martin-Castillo B, Dorca J, Vazquez-Martin A, et al: Incorporating the antidiabetic drug metformin in HER2-positive breast cancer treated with neo-adjuvant chemotherapy and trastuzumab: an ongoing clinical-translational research experience at the Catalan Institute of Oncology. Ann Oncol. 21:187–189. 2010. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang B, Liu L, Mao X and Zhang D: Effects of metformin on FOXM1 expression and on the biological behavior of acute leukemia cell lines. Mol Med Rep 10: 3193-3198, 2014.
APA
Zhang, B., Liu, L., Mao, X., & Zhang, D. (2014). Effects of metformin on FOXM1 expression and on the biological behavior of acute leukemia cell lines. Molecular Medicine Reports, 10, 3193-3198. https://doi.org/10.3892/mmr.2014.2629
MLA
Zhang, B., Liu, L., Mao, X., Zhang, D."Effects of metformin on FOXM1 expression and on the biological behavior of acute leukemia cell lines". Molecular Medicine Reports 10.6 (2014): 3193-3198.
Chicago
Zhang, B., Liu, L., Mao, X., Zhang, D."Effects of metformin on FOXM1 expression and on the biological behavior of acute leukemia cell lines". Molecular Medicine Reports 10, no. 6 (2014): 3193-3198. https://doi.org/10.3892/mmr.2014.2629
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang B, Liu L, Mao X and Zhang D: Effects of metformin on FOXM1 expression and on the biological behavior of acute leukemia cell lines. Mol Med Rep 10: 3193-3198, 2014.
APA
Zhang, B., Liu, L., Mao, X., & Zhang, D. (2014). Effects of metformin on FOXM1 expression and on the biological behavior of acute leukemia cell lines. Molecular Medicine Reports, 10, 3193-3198. https://doi.org/10.3892/mmr.2014.2629
MLA
Zhang, B., Liu, L., Mao, X., Zhang, D."Effects of metformin on FOXM1 expression and on the biological behavior of acute leukemia cell lines". Molecular Medicine Reports 10.6 (2014): 3193-3198.
Chicago
Zhang, B., Liu, L., Mao, X., Zhang, D."Effects of metformin on FOXM1 expression and on the biological behavior of acute leukemia cell lines". Molecular Medicine Reports 10, no. 6 (2014): 3193-3198. https://doi.org/10.3892/mmr.2014.2629
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team