Pharmacologic mechanisms underlying antidiabetic drug metformin's chemopreventive effect against colorectal cancer

In this review, current data was used to elucidate the mechanisms by which metformin hydrochloride exerts chemopreventive effects on colorectal cancer (CRC). The first-line agent for the treatment of type 2 diabetes mellitus (T2DM), metformin, has recently been cited in a number of studies, in vitro and in vivo, for its potential anticancer capabilities in a variety of malignancies. While generally known to target AMP-activated protein kinase (AMPK), as an antidiabetic agent, the mechanisms by which metformin confers anticancer properties, particularly in CRC, are far less understood. This review aims to comprehensively integrate novel pharmacologic findings, especially more recent insights, to explain metformin's anti-CRC mechanisms. Among these include metformin-mediated alterations to a number of key signaling pathways involving CRC cell growth and stemness, anti-EMT (epithelial-mesenchymal transition) regulatory actions, as well as altered pm-cancer cellular energetic states and survival. These findings may prove particularly meaningful in the fields of experimental and clinical oncotherapy.

Automated summary

Metformin hydrochloride, a first-line agent for treating type 2 diabetes mellitus, has shown potential anticancer capabilities, especially in colorectal cancer. It affects key signaling pathways and survival states through various mechanisms, targeting CRC cell growth, stemness, and processes related to metastasis.