Effects Of Folate Supplementation On Oral Cancer Prolieration

Based upon evidence of human health outcomes correlated with folic acid intake, the US Food and Drug Administration adopted requirements for folate fortification of foods that increased mean dietary folate intake and concomitantly decreased incidence of negative health outcomes associated with folate deficiency. Although folate can protect normal cells from turning cancerous, recent evidence suggests that supplementation may accelerate growth of existing colorectal cancers. Whether folate plays a similar and significant role in growth and proliferation of other slow developing cancers is unknown.

Objective: The purpose of this study was to examine the role of folate in growth and proliferation of slow developing cancers, such as oral cancer.

Method: Proliferative effects of folic acid on phenotypic behaviors of two well characterized oral cancer cell lines, CAL27 and SCC25, were evaluated in vitro. Results: Oral cancer cell proliferation in both was significantly enhanced (20-50%) in a dose-dependent manner by folic acid administration between 10 and 400 ug/mL, while no effects were noted on normal control cell lines. Cell viability was similarly increased over this concentration range. Genomic analysis revealed that neither oral cancer cell line harbored methylenetetrahydrofolate reductase polymorphisms, 677C>T or 1298A>C, previously associated with increased cancer risk. RT-PCR, however, revealed that folate administration increased mRNA expression of ornithine decarboxylase and c-myc in these cells, which are associated with oral cancer growth and progression.

Conclusions: This study is the first to directly examine the potential effects of folate on existing oral cancers. While other factors may initiate oral carcinogenesis, these results suggest folate may modulate the progression of the malignancy process in already transformed oral cancers. Determining the effects of dietary folate intake on the progression of oral cancers is an important step towards understanding factors which lead to more effective treatment options and improved health outcomes for patients.