Colorectal and Prostate Cancer Risk in Diabetes: Metformin, an Actor behind the Scene

Abstract

Both diabetes and cancer are prevalent diseases whose incidence rates are increasing worldwide, especially in countries that are undergoing rapid industrialization changes. Apparently, lifestyle risk factors including diet, physical inactivity and obesity play pivotal, yet preventable, roles in the etiology of both diseases. Epidemiological studies provide strong evidence that subjects with diabetes are at significantly higher risk of developing many forms of cancer and especially solid tumors. In addition to pancreatic and breast cancer, the incidence of colorectal cancer and prostate cancer is increased in type 2 diabetes. While diabetes (type 2) and cancer share many risk factors, the biological links between the two diseases are poorly characterized. In this review, we highlight the mechanistic pathways that link diabetes to colorectal and prostate cancer and the use of Metformin, a diabetes drug, to prevent and/or treat colorectal and prostate cancer. We review the role of AMPK activation in autophagy, oxidative stress, inflammation, apoptosis, and cell cycle progression.

Mechanistic Study of Inhibitory Effects of Metformin and Atorvastatin in Combination on Prostate Cancer Cells <i>in Vitro</i> and <i>in Vivo</i>

“…10,11) Finally, a recent study suggested statin use moderates the risk of prostate cancer among type II diabetic patients using metformin.…”

“…7) Further, epidemiologic evidence revealed a decreased incidence of prostate cancer in men taking metformin, 8,9) and both animal and in vitro models demonstrate its activity in prostate cancer cell lines. 10,11) Finally, a recent study suggested statin use moderates the risk of prostate cancer among type II diabetic patients using metformin. 12) Epidemiological studies have shown a reduced risk of advanced prostate cancer with the use of statins.…”

Comment on Goldsworthy et al. Haploinsufficiency of the Insulin Receptor in the Presence of a Splice-Site Mutation in Ppp2r2a Results in a Novel Digenic Mouse Model of Type 2 Diabetes. Diabetes 2016;65:1434–1446

“…Of importance, the risk of developing these tumor types is significantly higher in patients with type 2 diabetes. Lifestyle risk factors, including diet and obesity, play relevant roles in the etiology of both diseases (2). In fact, it has been recently reported that a high-fat diet and obesity increased the development and aggressiveness of breast cancer tumors in vivo and that the oral administration of FTY720 (fingolimod) suppressed these effects (3).…”

“…Thus, the antidiabetes drug metformin has been described to induce PP2A activity and potent antitumor effects in colorectal and prostate cancer, among others (2,8). However, a recent study reported that metformin could increase the risk of tauopathies in elderly patients with diabetes (9).…”

Avaliação do efeito citotóxico da metformina em linhagens celulares de adenocarcinoma de próstata e de feocromocitoma

“…Diversos estudos clínicos apontaram para associação entre o uso de metformina e a redução e prevenção na progressão em diferentes tipos de câncer (7,(59)(60)(61)(62)(63)(64)(65)(66) intrinsecamente observado nos tumores com mutações nas subunidades de SDH (succinato desidrogenase), pode representar um mecanismo interessante, cuja eficiência alvo direcionada merece ser melhor esclarecida.…”