We report here the single and combined antitumor activity on
B16 melanoma in female C57BL/6 X DBA/2F1 mice bearing s.c.
tumors of
sodium ascorbate,
carbidopa-levodopa methyl
ester, and dietary
phenylalanine and
tyrosine deficiency. Groups of 15 mice were fed continuously one of three test diets both with and without
sodium ascorbate (30 mg/ml) in the
drinking water beginning 2 weeks before inoculation of 10(6)
melanoma cells. The test diets included the following amounts of
tyrosine-
phenylalanine: commercial, 1.09 and 0.64%; purified, 0.6 and 0.3%; and deficient, 0.08 and 0.04%.
Drug-treated groups received daily
injections of
carbidopa (100 mg/kg) and
levodopa methyl ester (1000 mg/kg) i.p. for 15 days beginning 1 day after
tumor transplant.
Tumor growth curves and median survival time were determined. Ascorbate stimulated
tumor growth in the commercial diet group. In mice fed the purified diet, ascorbate inhibited growth in some
tumors, while it had no effect on others. Ascorbate inhibited
tumor growth in mice fed the deficient diet, which itself severely inhibited
tumor growth, and in this group increased survival by 82%.
Drug treatment had little effect on
tumor growth and survival of mice fed the commercial diet, but it significantly decreased growth and moderately increased survival of mice fed the purified diet. The deficient diet enhanced
drug activity and increased survival of
tumor-bearing mice by 73%. Combined
therapy had little effect in mice fed the commercial diet;l however, mice fed the purified diet and receiving
drug and ascorbate had smaller
tumors and lived 55% longer. In mice fed the deficient diet, the combination retarded
tumor growth and increased survival dramatically by 123%. These data indicate that adding ascorbate and restricting
tyrosine and
phenylalanine in combination with
levodopa methyl ester therapy may become an important strategy for treating
malignant melanoma.