Folic acid: friend or foe in cancer therapy

Abstract

Folic acid plays a crucial role in diverse biological processes, notably cell maturation and proliferation. Here, we performed a literature review using articles listed in electronic databases, such as PubMed, Scopus, MEDLINE, and Google Scholar. In this review article, we describe contradictory data regarding the role of folic acid in cancer development and progression. While some studies have confirmed its beneficial effects in diminishing the risk of various cancers, others have reported a potential carcinogenic effect. The current narrative review elucidates these conflicting data by highlighting the possible molecular mechanisms explaining each point of view. Further multicenter molecular and genetic studies, in addition to human randomized clinical trials, are necessary to provide a more comprehensive understanding of the relationship between folic acid and cancer.

Keywords: Breast cancer; carcinogenic; colorectal cancer; folate; folic acid; lung cancer; prostate cancer.

Figure 1.

Molecular mechanisms of the protective effect of folic acid against cancer. These mechanisms include its role in nucleotide synthesis, DNA methylation, homocysteine metabolism, DNA repair, and reduction of oxidative stress. ALDH1, Aldehyde Dehydrogenase 1; CYP2E1, Cytochrome P450 2E1.

Figure 2.

Molecular mechanisms of the carcinogenic potential of folic acid. CpG, Cytosine-phosphate-Guanine; E-Cadherin, Epithelial Cadherin; FR-α, folate receptor-alpha; FR-β, folate receptor-beta; MTHFR, methyltetrahydrofolate reductase; SHMT, serine hydroxymethyltransferase; SLC19A1, Solute Carrier Family 19 Member 1.