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Mechanisms of cancer cell killing by metformin: a review on different cell death pathways
Xiao-Yu Wu1, Wen-Wen Xu2, Xiang-Kun Huan1
1Department of Surgical Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China.
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.
Insights
Metformin, an antidiabetic drug, enhances cancer cell death and immune response, potentially overcoming therapy resistance. This review explores its role in various cell death pathways for improved cancer treatment.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Cancer therapy resistance is a major clinical challenge.
- Cancer cells evade treatment by suppressing cell death and anti-tumour immunity.
- Adjuvants can enhance anti-cancer therapy by stimulating cell death pathways.
Purpose of the Study:
- To review cellular and molecular mechanisms of cancer cell death induced by therapy.
- To discuss the modulatory effects of metformin on diverse cancer cell death pathways.
- To highlight metformin's potential in overcoming anti-cancer drug resistance.
Main Methods:
- Literature review of cellular and molecular mechanisms.
- Analysis of studies on metformin's impact on cancer cell death.
- Discussion of metformin's role in apoptosis, mitotic catastrophe, senescence, autophagy, ferroptosis, and pyroptosis.
Main Results:
- Metformin amplifies cell death, particularly apoptosis, in various cancer cells.
- Metformin stimulates the immune system, contributing to cancer cell death induction.
- Metformin modulates multiple cell death pathways, influencing therapy sensitivity.
Conclusions:
- Metformin shows promise as an adjuvant to enhance anti-cancer therapy efficacy.
- Understanding metformin's role in cell death mechanisms is crucial for improving cancer treatment outcomes.
- Targeting cell death pathways with agents like metformin may overcome cancer resistance.
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