Metformin: A Bridge between Diabetes and Prostate Cancer

Abstract

Prostate cancer (PCa) has become the most frequent type of cancer in men. Recent data suggest that diabetic patients taking metformin have a lower incidence of certain cancer, including PCa. Metformin is the most common drug used in type II diabetes mellitus; its use has been shown to lower the incidence of several cancers, although there are ambiguous data about the anticancer activity of metformin. A large number of studies examined the potential antineoplastic mechanism of metformin although it is not still completely understood. This review summarizes the literature concerning the effects of metformin on PCa cells, highlighting its numerous mechanisms of action through which it can act. We analyze the possible causes of the discordances regarding the impact of metformin on risk of PCa; we discuss the latest findings in this field, suggesting that metformin may have a future role in the management of PCa both as monotherapy and in combination with other drugs.

Impact of DPP4 Inhibitors in Survival of Patients With Prostate, Pancreas, and Breast Cancer

“…The role of metformin as an anti-tumor agent is wellestablished in many types of cancer including prostate cancer (23)(24)(25). Metformin has antineoplastic effects such as adenosine monophosphate-activated protein kinase (AMPK)-dependent suppression of androgen signaling pathway, and alterations of insulin-like growth factor-1 (IGF-1) signaling pathways that cause the growth and proliferation of prostate cancer.…”

Metformin inhibits prostate cancer growth induced by a high‐fat diet in Pten‐deficient model mice

“…In the TRAMP mouse model, metformin inhibited prostate cancer progression through inflammatory responses . These findings suggest that inhibition of prostate cancer progression by metformin might be mostly mediated by inflammation, whereas several reports showed that the mechanism was mediated by other pathways, including 5’ adenosine monophosphate‐activated protein kinase activation . Metformin has been shown to alter the tumor immune microenvironment, including macrophages, and suppress disease progression in obese pancreatic and breast cancer mouse models .…”

Metformin may offer no protective effect in men undergoing external beam radiation therapy for prostate cancer

“…Pre‐treatment of PC3 cells with the mTOR inhibitor rapamycin was shown to inhibit the accumulation of HIF1α . Further studies have shown that metformin inhibits mTOR via both AMPK‐dependent and ‐independent pathways ; therefore, we investigated whether metformin might reduce the expression of HIF1α in PC3 cells via inhibition of mTOR. As shown in Fig.…”