ArticleClinical and experimental medicine2025
Balancing the scales: folic acid and vitamin B12 in the aggressiveness of hepatocellular carcinoma.
Article in Clinical and experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Hepatocellular carcinoma represents a significant global cancer burden, ranking as the sixth most prevalent malignancy worldwide and constituting the third most frequent cause of cancer-related mortality. Folate and vitamin B12 play a crucial interdependent role in various physiological processes via their shared involvement in one-carbon metabolism. Most of the previous studies on patient cohorts have shown the association of levels of these vitamins with hepatocellular carcinoma progression and development. However, the combinatorial effect of folate and vitamin B12 on cancer hallmarks in HCC remains understudied. This study aims to determine the effects of an imbalance between folate and vitamin B12 in relation to HCC. HepG2 cells were cultured in media supplemented with varied levels of folic acid and vitamin B12 and were divided into five groups (BNFN, BDFO, FDBO, BNFO, and FNBO) (F-folic acid, B-vitamin B12, N-normal, D-deficient, O-over-supplemented), and various cancer hallmarks assays were performed. Cell migration assay revealed that the groups containing over-supplemented folic acid, irrespective of the levels of vitamin B12, showed increased migration, whereas migratory capacity was impeded in folic acid-deficient (FDBO) group. However, the invasion was increased in the groups FDBO and FNBO in association with a decrease in the percentage of viable cells and increased apoptosis. Interestingly, the number of spheres formed was considerably high in cells over- supplemented with folic acid (BDFO & BNFO), concordant with the results found in the migration assay. Altogether, this suggests that an imbalance of low vitamin B12 and abundant folate aggravates cancer by enhancing cancer stem cell survival. Thus, these observations suggest that maintaining a proper balance between vitamin B12 and folate is essential for regulating cellular processes and potentially mitigating cancer progression.
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