title: Folic acid and sodium butyrate prevent tumorigenesis in a mouse model of colorectal cancer.
abstract: Colorectal cancer is a leading cause of morbidity and mortality worldwide, and its incidence has been increasing in recent years. The role of epigenetic modifications, including DNA methylation and histone modifications, has only recently been investigated. In this study, the effects of epigenetic agents such as folic acid (FA) and sodium butyrate (NaBu) on the development of colorectal cancer induced by 1,2-dimethylhydrazine (DMH) using ICR mice was examined. Of the mice treated in a chemopreventive manner with epigenetic agents, FA and NaBu, 15-50% developed colorectal cancer at 24 weeks compared with a 95% incidence of colorectal cancer in DMH-treated control mice. Folate deficiency can alter cytosine methylation in DNA leading to inappropriate activation of the proto-oncogene c-myc. We detected lower levels of p21(WAF1) gene expression in colorectal cancer samples, as well as significantly lower levels of acetylated histone H3, compared with samples from corresponding normal colorectal mucosa. In contrast, administration of NaBu increased levels of p21(WAF1) mRNA and p21(WAF1) protein, and was associated with an accumulation of histone acetylation. In summary, our results show that FA and NaBu reduce the incidence of colorectal cancer induced by DMH-induced in ICR mice, and therefore we hypothesize that targeting epigenetic targets should be further investigated for the prevention of colorectal cancer in humans.
authors.affiliation: Shanghai Jiaotong University School of Medicine Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Lu
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Dan-Feng
authors.initials: DF
authors.lastname: Sun
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tian
authors.forename: Shu-Liang
authors.initials: SL
authors.lastname: Zhao
authors.forename: Ying-Xuan
authors.initials: YX
authors.lastname: Chen
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016017:Odds Ratio; D011401:Promoter Regions, Genetic / Q000235:genetics; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D002087:Butyrates; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006657:Histones; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D005492:Folic Acid