Hypoxia-Induced Changes in L-Cysteine Metabolism and Antioxidative Processes in Melanoma Cells

This study was performed on human primary (WM115) and metastatic (WM266-4) melanoma cell lines developed from the same individual. The expression of proteins involved in L-cysteine metabolism (sulfurtransferases, and cystathionine beta-synthase) and antioxidative processes (thioredoxin, thioredoxin reductase-1, glutathione peroxidase, superoxide dismutase 1) as well as the level of sufane sulfur, and cell proliferation under hypoxic conditions were investigated. Hypoxia in WM115 and WM266-4 cells was confirmed by induced expression of carbonic anhydrase IX and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 by the RT-PCR and Western blot methods. It was shown that, under hypoxic conditions the inhibition of WM115 and WM266-4 melanoma cell proliferation was associated with decreased expression of thioredoxin reductase-1 and cystathionine beta-synthase. These two enzymes may be important therapeutic targets in the treatment of melanoma. Interestingly, it was also found that in normoxia the expression and activity of 3-mercaptopyruvate sulfurtransferase in metastatic WM266-4 melanoma cells was significantly higher than in primary melanoma WM115 cells.

Automated summary

This study investigates the expression of proteins involved in L-cysteine metabolism and antioxidative processes, as well as cell proliferation under hypoxic conditions in human melanoma cell lines. The results suggest that the inhibition of melanoma cell proliferation under hypoxia is associated with decreased expression of thioredoxin reductase-1 and cystathionine beta-synthase, which may have significance in melanoma treatment. Interestingly, it was found that the expression and activity of 3-mercaptopyruvate sulfurtransferase is significantly higher in metastatic melanoma cells than in primary melanoma cells under normoxia.