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Metformin as an anti-cancer agent: actions and mechanisms targeting cancer stem cells
1Julius L. Chambers Biomedical/Biotechnology Research Institute, Department of Biological and Biomedical Sciences, North Carolina Central University, North Carolina Research Campus, Kannapolis, NC 28081, USA.
Abstract:
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse. Studies using various cancer models, including breast, pancreatic, prostate, and colon, have demonstrated the potency of metformin in attenuating CSCs through the targeting of specific pathways involved in cell differentiation, renewal, metastasis, and metabolism. In this review, we provide a comprehensive overview of the anti-cancer actions and mechanisms of metformin, including the regulation of CSCs and related pathways. We also discuss the potential anti-cancer applications of metformin as mono- or combination therapies.
Insights
Metformin, a diabetes drug, shows anti-cancer potential by targeting cancer stem cells (CSCs) and impairing tumor metabolism. This review explores its mechanisms and therapeutic applications in various cancers.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Metformin, a type II diabetes drug, exhibits anti-cancer properties observed in epidemiological studies.
- Preclinical research indicates metformin affects cellular metabolism and oncogenic signaling pathways (receptor tyrosine kinase, PI3K/Akt, mTOR).
Purpose of the Study:
- To review the anti-cancer actions and mechanisms of metformin.
- To focus on metformin's effects on cancer stem cells (CSCs) and related pathways.
- To discuss potential therapeutic applications of metformin in cancer treatment.
Main Methods:
- Review of preclinical studies and cancer models (breast, pancreatic, prostate, colon).
- Analysis of metformin's impact on CSCs, differentiation, renewal, metastasis, and metabolism.
- Examination of signaling pathways regulated by metformin.
Main Results:
- Metformin demonstrates inhibitory effects on cancer stem cells (CSCs).
- It targets key pathways involved in CSCs, impacting tumor metastasis, drug resistance, and relapse.
- Studies show metformin's potency across various cancer types.
Conclusions:
- Metformin possesses significant anti-cancer potential, particularly through CSC regulation.
- Its mechanisms involve metabolic disruption and suppression of oncogenic pathways.
- Metformin shows promise as a monotherapy or in combination treatments for cancer.
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