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Review
. 2023 Jan;478(1):197-214.
doi: 10.1007/s11010-022-04502-4. Epub 2022 Jun 30.

Mechanisms of cancer cell killing by metformin: a review on different cell death pathways

Xiao-Yu Wu #  1 , Wen-Wen Xu #  2 , Xiang-Kun Huan  1 , Guan-Nan Wu  1 , Gang Li  3 , Yu-Hong Zhou  4 , Masoud Najafi  5
Affiliations
Review

Mechanisms of cancer cell killing by metformin: a review on different cell death pathways

Xiao-Yu Wu et al. Mol Cell Biochem. 2023 Jan.

Abstract

Cancer resistance to anti-tumour agents has been one of the serious challenges in different types of cancer treatment. Usually, an increase in the cell death markers can predict a higher rate of survival among patients diagnosed with cancer. By increasing the regulation of survival genes, cancer cells can display a higher resistance to therapy through the suppression of anti-tumour immunity and inhibition of cell death signalling pathways. Administration of certain adjuvants may be useful in order to increase the therapeutic efficiency of anti-cancer therapy through the stimulation of different cell death pathways. Several studies have demonstrated that metformin, an antidiabetic drug with anti-cancer properties, amplifies cell death mechanisms, especially apoptosis in a broad-spectrum of cancer cells. Stimulation of the immune system by metformin has been shown to play a key role in the induction of cell death. It seems that the induction or suppression of different cell death mechanisms has a pivotal role in either sensitization or resistance of cancer cells to therapy. This review explains the cellular and molecular mechanisms of cell death following anticancer therapy. Then, we discuss the modulatory roles of metformin on different cancer cell death pathways including apoptosis, mitotic catastrophe, senescence, autophagy, ferroptosis and pyroptosis.

Keywords: Apoptosis; Autophagy; Cancer; Cell death; Metformin; Senescence.

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References

    1. Wang L-H, Wu C-F, Rajasekaran N, Shin YK (2018) Loss of tumor suppressor gene function in human cancer: an overview. Cell Physiol Biochem 51(6):2647–2693 - DOI
    1. Jimbo H, Nagai H, Fujiwara S, Shimoura N, Nishigori C (2020) Fas-FasL interaction in cytotoxic T cell-mediated vitiligo: the role of lesional expression of tumor necrosis factor-α and interferon-γ in Fas-mediated melanocyte apoptosis. Exp Dermatol 29(1):61–70 - DOI
    1. Mu Q, Najafi M (2021) Modulation of the tumor microenvironment (TME) by melatonin. Eur J Pharmacol 907:174365. https://doi.org/10.1016/j.ejphar.2021.174365 - DOI
    1. Farhood B, Hoseini-Ghahfarokhi M, Motevaseli E, Mirtavoos-Mahyari H, Musa AE, Najafi M (2020) TGF-β in radiotherapy: mechanisms of tumor resistance and normal tissues injury. Pharmacol Res 155:104745 - DOI
    1. Mu Q, Najafi M (2021) Resveratrol for targeting the tumor microenvironment and its interactions with cancer cells. Int Immunopharmacol 98:107895. https://doi.org/10.1016/j.intimp.2021.107895 - DOI

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