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

被引:32
作者
Petersen, Lars F. [1 ]
Brockton, Nigel T. [2 ]
Bakkar, Ashraf [1 ,3 ]
Liu, Shuhong [1 ]
Wen, Jing [4 ]
Weljie, Aalim M. [4 ]
Bismar, Tarek A. [1 ,5 ,6 ]
机构
[1] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2V 1P9, Canada
[2] Alberta Hlth Serv Canc Care, Div Populat Hlth Res, Calgary, AB, Canada
[3] Sinai Univ, Fac Dent, Dept Biochem, Sinai, Egypt
[4] Univ Calgary, Dept Biol Sci, Calgary, AB T2V 1P9, Canada
[5] Tom Baker Canc Clin, So Alberta Canc Res Inst, Calgary, AB, Canada
[6] Segal Canc Ctr, Montreal, PQ, Canada
关键词
prostate cancer; folic acid; invasion; metabolomics; sarcosine; GLYCINE N-METHYLTRANSFERASE; MEMBRANE ANTIGEN PSMA; FOLATE-DEFICIENCY; DNA METHYLATION; EXPRESSION; RISK; SARCOSINE; DIET; PREVENTION; ANEUPLOIDY;
D O I
10.1111/j.1464-410X.2011.10437.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:788 / 795
页数:8
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