L-cyst(e)ine requirements of malignant cells and progress toward depletion therapy.
The L-cyst(e)ine requirements of normal and malignant cells are reviewed and expanded within the context of establishing whether the measurement of gamma-cystathionase levels constitutes a predictive test for tumor sensitivity to L-cyst(e)ine depletion. The ability of both purified L-cysteine desulfhydrase and gamma-cystathionase to inhibit the growth of the L-cystine-dependent L1210 leukemia in culture is presented, as well as approaches to circumvent the limitations of these enzymes for in vivo therapy. The ability of proparagylglycine to inhibit L-cysteine biosynthesis in vivo is reviewed for its possible use in combination therapy. In addition, the ability of poly D,L-alanine modification of Escherichia coli L-asparaginase to increase the plasma half-life in mice tenfold as well as to decrease the immunogenicity of the enzyme is presented.
D000818:Animals; D000917:Antibody Formation; D001215:Asparaginase / Q000494:pharmacology; D002460:Cell Line; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D003545:Cysteine / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000378:metabolism; D003553:Cystine / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism
D004791:Enzyme Inhibitors; D003553:Cystine; D001215:Asparaginase; D003542:Cystathionine gamma-Lyase; D003545:Cysteine