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REVIEW article

Front. Oncol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1455492

Metformin and Its Potential Influence on Cell Fate Decision between Apoptosis and Senescence in Cancer, with a Special Emphasis on Glioblastoma

Provisionally accepted
Melika Hajimohammadebrahim-Ketabforoush Melika Hajimohammadebrahim-Ketabforoush 1*Alireza Zali Alireza Zali 2Mohammadreza Shahmohammadi Mohammadreza Shahmohammadi 2Amir A. Hamidieh Amir A. Hamidieh 3
  • 1 National Nutrition and Food Technology Research Institute, Tehran, Iran
  • 2 Shahid Beheshti University of Medical Sciences, Tehran, Tehran, Iran
  • 3 Tehran University of Medical Sciences, Tehran, Tehran, Iran

The final, formatted version of the article will be published soon.

    Despite reaching enormous achievements in therapeutic approaches worldwide, GBM still remains the most incurable malignancy among various cancers. It emphasizes the necessity of adjuvant therapies from the perspectives of both patients and healthcare providers. Therefore, most emerging studies have focused on various complementary and adjuvant therapies. Among them, metabolic therapy has received special attention, and metformin has been considered as a treatment in various types of cancer, including GBM. It is clearly evident that reaching efficient approaches without a comprehensive evaluation of the key mechanisms is not possible. Among the studied mechanisms, one of the more challenging ones is the effect of metformin on apoptosis and senescence. Moreover, metformin is well known as an insulin sensitizer. However, if insulin signaling is facilitated in the tumor microenvironment, it may result in tumor growth. Therefore, to partially resolve some paradoxical issues, we conducted a narrative review of related studies to address the following questions as comprehensively as possible: 1) Does the improvement of cellular insulin function resulting from metformin have detrimental or beneficial effects on GBM cells? 2) If these effects are detrimental to GBM cells, which is more important: apoptosis or senescence? 3) What determines the cellular decision between apoptosis and senescence?

    Keywords: Metformin, GBM, Apoptosis, senescence, calorie restriction, AMPK, mTOR, p53

    Received: 26 Jun 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Hajimohammadebrahim-Ketabforoush, Zali, Shahmohammadi and Hamidieh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Melika Hajimohammadebrahim-Ketabforoush, National Nutrition and Food Technology Research Institute, Tehran, Iran

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.