Skip to main content
padlock icon - secure page this page is secure

Antidiabetic Drug Metformin Induces Apoptosis in Human MCF Breast Cancer via Targeting ERK Signaling

Buy Article:

$46.00 + tax (Refund Policy)

Metformin is the most widely used antidiabetic drug for type II diabetes in the world. Recent studies provide clues that the use of metformin may be associated with reduced incidence and improved prognosis of certain cancers and there is increasing evidence of a potential efficacy of this agent as an anticancer drug. This observation led us to hypothesize that metformin might inhibit human breast cancer cells (MCF-7) growth. Here, we report that metformin induced apoptosis in human breast carcinoma cell lines MCF-7 cells via novel signaling pathway. Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2. Inhibitors of signaling proteins were used to study the mechanism(s) of metformin function. Receptor inhibitor studies indicated that p53 activation was mediated through insulin receptor (IR), not insulin-like growth factor-1 receptor (IGF-1R). Furthermore, MEK inhibitor significantly suppressed metformin-induced p53 and Bax elevation while ERK inhibitor generated a slight reduction in p53 levels. In contrast, PI3K inhibitor did not produce any effect on the metformin-elevated p53 levels. Finally, SAPK/JNK, known to be involved in apoptosis, was activated in cells treated with metformin and the activation appeared to occur downstream of ERK. All these results suggested that metformin activated p53, Bax, and induced tumor cell apoptosis through the ERK signaling pathway. This pathway has not been previously described for IR, p53, Bax activation, or apoptosis. Metformin, a novel inducer of apoptosis, and its analogs may offer a novel strategy for the treatment of cancer cells.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
No Metrics

Keywords: Bax; Breast cancer; ERK; JNK; Metformin; p21; p53

Document Type: Research Article

Publication date: June 1, 2011

More about this publication?
  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.

    From Volume 23, Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics is Open Access under the terms of the Creative Commons CC BY-NC-ND license.

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more