Metformin and Colorectal Cancer

AMABLE, G; MARTÍNEZ-LEÓN, EDUARDO; PICCO, M E; REY O

BIOCELL

Tech Science Press

Lugar: Nevada; Año: 2022 vol. 46 p. 51 - 59

0327-9545

Colorectal cancer (CRC) is one of the maincauses of cancer-related mortality in the developed world despite recentdevelopments in detection and treatment. Several epidemiological studies indicate thatmetformin, a widely prescribed antidiabetic drug, exerts a protective effect ondifferent cancers including CRC.  Furthermore, a recentdouble-blind placebo-controlled, randomized trial showed that metforminsignificantly decreased colorectal adenoma recurrence.  Studies exploring themechanism of action of metformin in cells derived from different types of cancersreported many effects including respiratory chain complex 1 inhibition, Aktphosphorylation inhibition, ATP depletion, PKA activation and Wnt signaling inhibition.  However, many of these results were obtainedemploying metformin at concentrations several fold higher than those achievedin target tissues in diabetic patients receiving therapeutic recommended dosesof metformin.  In contrast, recentstudies obtained with metformin at concentrations compatible with thosedetected in human intestines revealed that metforminelicit responses that target β-catenin,PI3K/Akt, E-cadherin, p120-catenin and focal adhesion kinase which are key molecules and signaling pathwaysassociated to colorectal cancer development.  Thisbrief review revisit several know aspects as well as novel ones on the effectsof metformin on cancer cells.@font-face{font-family:"ＭＳ 明朝";panose-1:0 0 0 0 0 0 0 0 0 0;mso-font-charset:128;mso-generic-font-family:roman;mso-font-format:other;mso-font-pitch:fixed;mso-font-signature:1 134676480 16 0 131072 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman";}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:Cambria;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}div.WordSection1{page:WordSection1;}