Human Tumor Growth in Nude Mice Is Associated with Decreased Plasma Cysteine and Homocysteine

Abstract

The methionine cycle and its metabolites homocysteine and cysteine serve several important functions in cellular metabolism. Abnormalities in metabolism of the methionine cycle have been associated with cancer. We determined plasma levels of methionine, homocysteine and cysteine in nude mice implanted with human cancer cell lines (MDA-MB-435 breast, PC-3 prostate, HT29 colon, BX-PC3 pancreas) over a prolonged period of tumor growth. The data were compared with correspondins values in nontumor-bearing controls. Nude mice were injected s.c. in the right flank with 10⁶ cancer cells. Tumor growth was measured over time. Methionine was measured in plasma by HPLC. Cysteine and homocysteine were measured in plasma by recombinant enzyme assays and spectrophotometry to measure products. The concentrations of cysteine and homocysteine in plasma decreased significantly as a result of progression of breast, prostate and the pancreas tumor types implanted in the nude mice at least over a two-month period. Data for the colon tumors were nonsignificant for both cysteine and homocysteine. In the case of methionine, the decrease was significant only due to progression of the breast tumors, grown over a long time period, as compared to the mice without tumors control. The results suggest that sulphur amino acids may be plasma or serum biomarkers for cancer progression.