The anticancer potential of metformin on prostate cancer

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.