Metformin and antineoplastic action

Abstract

Metformin is the most frequently used drug in treatment of type 2 diabetes, particularly in obese patients. One of the potential mechanisms for his beneficial metabolic effect is activation of AMP-activated protein kinase (AMPK). AMPK is one of the key players in regulation of energy homeostasis, especially in skeletal muscles, liver and adipose tissue. Exercise, adiponectin and leptin are some of the activators of this pathway stimulating increased glucose uptake by increased GLUT-4 translocation to plasma membrane. LKB1, the upstream kinase in this pathway, is the tumor suppressor expected to inhibit initiation/growth of tumors and the activator of phosphorylation of threonin-172 of AMPK. Thus, AMPK pathway is meeting point of biochemical pathways mediating energy homeostasis and those mediating suppression of tumor genesis. We may speculate that activation of AMPK using metformin will inhibit LKB1 sensitive tumor initiation/growth. In vitro studies have shown reduced basal proliferation rate as well as abolished stimulation of breast cancer cell line with IGF-I or insulin induced marked cell proliferation during incubation with metformin. A few clinical studies reported reduced incidence of neoplastic diseases in diabetic patients treated with metforminin in comparison to diet or other antidiabetic agents. In conclusion, we may speculate that metformin could have antineoplastic effect, especially in LKB1 sensitive tumors (breast, prostate, ovary). © 2009 Nova Science Publishers, Inc.