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The anticancer potential of metformin on prostate cancer

Prostate Cancer and Prostatic Diseases (2019) | Download Citation

Abstract

Background

Prostate cancer (PCa) is characterized as the most frequent type of cancer in males. Recent research has suggested patients who have diabetes mellitus taking metformin (MF) have a lower risk of PCa. MF has antineoplastic effects such as adenosine monophosphate-activated protein kinase (AMPK)-dependent and independent mechanisms, suppression of androgen signaling pathway, and alterations of insulin-like growth factor-1 (IGF-1) signaling pathways that cause the growth and proliferation of PCa. Based on epidemiological factors, patients with diabetes mellitus may have a protective effect on PCa.

Methods

A literature search on MEDLINE® was conducted using a combined query of “prostate cancer” and "metformin" to yield publications unveiling the mechanisms of action, biological effects, epidemiological evidence, and research advances of MF with respect to PCa.

Results

Evidence has shown that MF has multiple antineoplastic effects through AMPK-dependent and independent mechanisms, the alteration of IGF-1 signaling pathways, suppression of the androgen receptor pathway, inhibition of the mTOR pathway, and lipogenesis. Conduction of meta-analysis suggests mortality benefit to patients who exhibit PCa when taking MF. Clinical trials have shown evidence, demonstrating MF to improving significantly.

Conclusions

Herewith we review the literature regarding the numerous mechanisms of action of MF on PCa in order to decrease or repress the growth, proliferation, and differentiation of PCa cells. We analyze the molecular impacts of MF as well as adjunct therapies such as androgen deprivation therapy, aspirin, statin, or chemotherapy, proposing that MF may have a future role in the treatment protocol of PCa whether as a monotherapy or in combination with other drugs.

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Acknowledgements

The authors are thankful to Drs. Kelly Warren, Inefta Reid, Todd Miller, and Peter Brink for departmental support, as well as Mrs. Wendy Isser and Ms. Grace Garey for literature retrieval.

Author information

Affiliations

  1. Department of Physiology and Biophysics, Stony Brook Medicine, Stony Brook, NY, USA

    • Saher Zaidi
    • , Jason Gandhi
    •  & Sardar Ali Khan
  2. Medical Student Research Institute, St. George’s University School of Medicine, Grenada, Grenada

    • Jason Gandhi
  3. Department of Internal Medicine, Stony Brook Southampton Hospital, Southampton, NY, USA

    • Gunjan Joshi
  4. Foley Plaza Medical, New York, NY, USA

    • Noel L. Smith
  5. Department of Urology, Stony Brook Medicine, Stony Brook, NY, USA

    • Sardar Ali Khan

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Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Sardar Ali Khan.

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DOI

https://doi.org/10.1038/s41391-018-0085-2

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