Tumor therapy by deprivation of L-methionine: rationale and results.

Published reports indicate that normal rodent cells can grow in medium containing either L-methionine or L-homocysteine, whereas malignant rodent cells have an absolute requirement for L-methionine. Our studies with two normal human cell lines (fetal lung fibroblasts and bladder epithelial cells) exhibit equal growth in media containing either L-methionine or L-homocysteine. The same is true for five malignant human cell lines (carcinoma of the cervix [HeLa], adenocarcinoma of the breast [AlAb], acute lymphoblastic leukemia [MOLT-3], Wilms' tumor [SK-NEP-1], and reticulum cell sarcoma [T-77], whereas four other malignant cell lines (adenocarcinoma of the breast [SK-BR-2-III], the two lymphoblastic leukemias [CCRF-HSB-2 and CCRF-SB], and a neuroblastoma [SK-N-MC]) have absolute requirements for L-methionine. Two malignant cell lines, an adenocarcinoma of the lung (A549) and an adenocarcinoma of the pancreas (Capan-1), showed restricted growth under the experimental conditions used. L-Methionlinase (L-methionine-alpha-deamino-gamma-mercaptomethane-lyase, EC 4.4.1.11) at a concentration of 0.1 unit/ml leads to complete growth inhibition of cell cultures of both the normal human fetal lung fibroblasts (F-136-35-56) and the acute lymphoblastic leukemia (CCRF-HSB-2). L-Homocysteine-thiolactone in medium containing L-methioninase could partly "rescue" the normal but not the malignant cells.