High sensitivity of human melanoma cell lines to the growth inhibitory activity of mycoplasmal arginine deiminase in vitro.
Arginine deiminase (AD) is a potent growth inhibitor for some but not all tumour cell lines in vitro. As AD catalyses the direct conversion of L-arginine to L-citrulline, the AD-sensitivity of various tumour cells might be attributed to the levels of urea cycle enzymes involved in L-arginine biosynthesis. This study demonstrated that human melanoma cells were highly sensitive to the growth inhibitory activity of AD. Five melanoma cell lines tested also exhibited reduced argininosuccinate synthetase (ASS) gene expression--being almost absent in four cell lines and at low level in one cell line. This resulted in an inability of the cells to utilize L-citrulline for growth. Based on the tissue-specific regulation of ASS gene, the feature of melanomas suggests that it might be possible to develop agents with strong AD activity for chemotherapeutic use for human melanomas in vivo.
Sugimura
K
K
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Ohno
T
T
Kusuyama
T
T
Azuma
I
I
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001124:Argininosuccinate Synthase / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000494:pharmacology*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006867:Hydrolases / Q000494:pharmacology*; D008545:Melanoma / Q000473:pathology*; D008969:Molecular Sequence Data; D009174:Mycoplasma / Q000201:enzymology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014508:Urea / Q000378:metabolism
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D009363:Neoplasm Proteins; D014508:Urea; D006867:Hydrolases; C019723:arginine deiminase; D001124:Argininosuccinate Synthase