Title:The Potential Therapeutic Impact of Metformin in Glioblastoma
Multiforme
Volume: 30
Issue: 7
Author(s): Mehdi Sanati, Samaneh Aminyavari, Hamid Mollazadeh, Ali Motamed-Sanaye, Bahram Bibak, Elmira Mohtashami, Yong Teng, Amir R. Afshari*Amirhossein Sahebkar*
Affiliation:
- Department of Physiology and Pharmacology, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Medicine, The University of Western Australia, Perth, Australia
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Keywords:
Glioblastoma multiforme, metformin, anticancer, AMPK, proliferation, cancer.
Abstract: In terms of frequency and aggressiveness, glioblastoma multiforme (GBM) is
undoubtedly the most frequent and fatal primary brain tumor. Despite advances in clinical
management, the response to current treatments is dismal, with a 2-year survival rate
varying between 6 and 12 percent. Metformin, a derivative of biguanide widely used in
treating type 2 diabetes, has been shown to extend the lifespan of patients with various
malignancies. There is limited evidence available on the long-term survival of GBM
patients who have taken metformin. This research examined the literature to assess the
connection between metformin's anticancer properties and GBM development. Clinical
findings, together with the preclinical data from animal models and cell lines, are included
in the present review. This comprehensive review covers not only the association of
hyperactivation of the AMPK pathway with the anticancer activity of metformin but also
other mechanisms underpinning its role in apoptosis, cell proliferation, metastasis, as
well as its chemo-radio-sensitizing behavior against GBM. Current challenges and future
directions for developments and applications of metformin-based therapeutics are also
discussed.