title: Effects of metformin, buformin, and phenformin on the post-initiation stage of chemically induced mammary carcinogenesis in the rat.
abstract: Metformin is a widely prescribed drug for the treatment of type II diabetes. Although epidemiologic data have provided a strong rationale for investigating the potential of this biguanide for use in cancer prevention and control, uncertainty exists whether metformin should be expected to have an impact in nondiabetic patients. Furthermore, little attention has been given to the possibility that other biguanides may have anticancer activity. In this study, the effects of clinically relevant doses of metformin (9.3 mmol/kg diet), buformin (7.6 mmol/kg diet), and phenformin (5.0 mmol/kg diet) were compared with rats fed control diet (AIN93-G) during the post-initiation stage of 1-methyl-1-nitrosourea-induced (50 mg/kg body weight) mammary carcinogenesis (n = 30/group). Plasma, liver, skeletal muscle, visceral fat, mammary gland, and mammary carcinoma concentrations of the biguanides were determined. In comparison with the control group, buformin decreased cancer incidence, multiplicity, and burden, whereas metformin and phenformin had no statistically significant effect on the carcinogenic process relative to the control group. Buformin did not alter fasting plasma glucose or insulin. Within mammary carcinomas, evidence was obtained that buformin treatment perturbed signaling pathways related to energy sensing. However, further investigation is needed to determine the relative contributions of host systemic and cell autonomous mechanisms to the anticancer activity of biguanides such as buformin.
authors: Cancer Prevention Laboratory, Colorado State University, Fort Collins, Colorado.
authors: Zongjian
authors: Z
authors: Zhu
authors: Cancer Prevention Laboratory, Colorado State University, Fort Collins, Colorado.
authors: Weiqin
authors: W
authors: Jiang
authors: Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
authors: Matthew D
authors: MD
authors: Thompson
authors: Cancer Prevention Laboratory, Colorado State University, Fort Collins, Colorado.
authors: Dimas
authors: D
authors: Echeverria
authors: Cancer Prevention Laboratory, Colorado State University, Fort Collins, Colorado.
authors: John N
authors: JN
authors: McGinley
authors: Cancer Prevention Laboratory, Colorado State University, Fort Collins, Colorado. henry.thompson@colostate.edu.
authors: Henry J
authors: HJ
authors: Thompson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002026:Buformin / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008687:Metformin / Q000494:pharmacology*; D010629:Phenformin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002273:Carcinogens; D007004:Hypoglycemic Agents; D008687:Metformin; D010629:Phenformin; D002026:Buformin