Folic acid reduces nuclear translocation of beta-catenin in rectal mucosal crypts of patients with colorectal adenomas.
We have demonstrated that folic acid inhibits cell proliferation and epidermal growth factor receptor (EGFR) activation in colon cancer cell lines. We examined the effect of one year supplemental folic acid (5 mg/day) on the rectal mucosal expression of beta-catenin and pGSK3beta, known to be affected by EGF-R, in patients with colorectal adenomas. Folic acid treatment significantly reduced nuclear expression of beta-catenin (P < 0.05) and cellular expression of pGSK3beta (P < 0.01) when compared to placebo. Folic acid may exert its chemopreventive effect, at least in part, through inhibition of nuclear translocation of beta-catenin.
Jaszewski
Richard
R
Division of Gastroenterology, and Department of Internal Medicine, Veterans Affairs Medical Center, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Millar
Brett
B
Hatfield
James S
JS
Nogothu
Kiran
K
Finkenauer
Raphaela
R
Rishi
Arun K
AK
Naumoff
Jo Anne
JA
Kucuk
Omer
O
Axelrod
Bradley N
BN
Majumdar
Adhip P N
AP
D000236:Adenoma / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D002467:Cell Nucleus / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D019587:Dietary Supplements; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D010865:Pilot Projects; D010919:Placebos; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D010919:Placebos; D015534:Trans-Activators; D051176:beta Catenin; D005492:Folic Acid; D066246:ErbB Receptors; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3