Elevated physiological levels of folic acid can increase in vitro growth and invasiveness of prostate cancer cells

What's known on the subject? and What does the study add? Evidence has emerged identifying folic acid supplementation as a potential risk factor for cancer development or progression. Long‐term folic acid supplementation has been shown to increase the risk of prostate cancer development by three‐fold. Sarcosine is a byproduct of folate metabolism and has been proposed as a biomarker for aggressive prostate cancer phenotypes. We looked at the effects of physiologically relevant levels of folic acid on in vitro prostate cancer cell growth and invasion, and demonstrated that higher levels can have the effect of increasing both of these biological processes. We also show that these changes toward a more aggressive phenotype are not linked to increased sarcosine levels, however other metabolic pathways may be involved.

OBJECTIVES

• ? To investigate the effects of different folic acid concentrations on the growth and invasiveness of prostate cancer cell lines.
• ? To determine if observed changes are correlated with changes in levels of the potential prostate cancer biomarker, sarcosine, a byproduct of folate metabolism.

MATERIALS AND METHODS

• ? The prostate cancer cell lines PC‐3, LNCaP and DU145 were cultured in media containing 4, 20 or 100 nm of folic acid and assayed for growth over 9 days by counting viable cells at 3‐day intervals, or for invasion by passage through a Matrigel‐coated transwell membrane.
• ? Cells grown in the different folic acid media were collected and subjected to metabolomic analysis by gas chromatography and mass spectrometry to measure levels of intracellular sarcosine.

RESULTS

• ? The results show that higher levels of folic acid can increase cell growth in PC‐3 and LNCaP prostate cancer cell lines, and may also increase the invasive capacity of PC‐3, LNCaP and DU145 cells.
• ? We did not observe a correlation between increased invasion from higher folic acid concentrations and levels of sarcosine, but there were significant changes in other metabolites in cells grown in higher levels of folic acid.

CONCLUSION

• ? These findings suggest that folic acid has an important and potentially negative role in prostate cancer progression.