title: Folate supplementation induces differential dose-dependent modulation of proliferative phenotypes among cancerous and noncancerous oral cell lines in vitro.
abstract: Sufficient folate intake confers positive health benefits, while deficiency is linked with many health problems. Although the US policy of dietary folic acid fortification has reduced the incidence of these deficiency-related health problems, recent evidence has demonstrated an association between folic acid supplementation and increased colorectal cancer incidence. Few studies have explored the possibility that folate affects other slowly developing cancers. This study sought to determine whether folic acid supplementation is sufficient to alter the growth and development of existing oral cancers. A series of in vitro growth, viability, and adhesion assays were performed using the well-characterized human oral squamous cell carcinoma cell lines, CAL27 and SCC25, to determine the effects of folic acid supplementation. Folic acid administration significantly stimulated CAL27 and SCC25 proliferation in a dose-dependent manner, but it was not sufficient to increase proliferation at any concentration tested in the normal control cell line, HGF-1. Neither oral cancer cell line harbored the common C677T DNA polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene, which might reduce folate bioavailability. Overexpression of p53 mRNA was observed in both cancerous cell lines, but it was differentially altered by folic acid administration in only SCC25 cells. These findings suggest folic acid administration may significantly alter growth of oral cancers in vitro via p53-dependent and p53-independent pathways. As oral cancer rates continue to rise in specific geographic areas, and among specific subsets of the US population, understanding environmental mediators, such as folic acid supplementation, becomes increasingly important for nutrition and public health scientists.
authors.affiliation: Department of Biomedical Sciences, School of Dental Medicine, University of Nevada, Las Vegas, NV 89154, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McCabe
authors.forename: Sarah
authors.initials: S
authors.lastname: Chang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hajibandeh
authors.forename: Michael D
authors.initials: MD
authors.lastname: Tran
authors.forename: Colby A
authors.initials: CA
authors.lastname: Meeder
authors.forename: Kanika
authors.initials: K
authors.lastname: Sharma
authors.forename: Dieu-Hoa
authors.initials: DH
authors.lastname: Nguyen
authors.forename: Michael
authors.initials: M
authors.lastname: Moody
authors.forename: Mark A
authors.initials: MA
authors.lastname: Keiserman
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Bergman
authors.forename: Karl
authors.initials: K
authors.lastname: Kingsley
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019587:Dietary Supplements / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005492:Folic Acid / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014803:Vitamin B Complex / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D014803:Vitamin B Complex; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)