Ascorbate in the treatment of experimental transplanted melanoma.
Sodium ascorbate supplementation in drinking water inhibited subcutaneous tumor growth, enhanced levodopa methylester (LDME) chemotherapy, and increased survival of B16 melanoma-bearing mice. Antitumor activity was greatest in mice fed diets low in tyrosine and phenylalanine (restricted diet). Ascorbate partially protected against LDME-induced decrease in food intake. Primary tumor masses were smaller, more well defined, and less invasive in ascorbate-supplemented mice, and secondary tumor masses appeared encapsulated. Dehydroascorbate increased tumor growth and decreased survival. Ascorbate supplementation did not alter establishment of experimental B16-BL6 melanoma metastases but inhibited tumor outgrowth when combined with LDME chemotherapy and the restricted diet. Spontaneous metastasis was inhibited by ascorbate in mice fed the restricted diet. Ascorbate supplementation doubled plasma concentration in melanoma-bearing mice independent of diet and increased tumor concentration 3.7-fold (basal diet) and 5.6-fold (restricted diet) relative to unsupplemented mice. Tumor peroxidation also increased during ascorbate supplementation and LDME treatment.
Meadows
G G
GG
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman 99164-6510.
Pierson
H F
HF
Abdallah
R M
RM
D000818:Animals; D001205:Ascorbic Acid / Q000097:blood / Q000494:pharmacology*; D003683:Dehydroascorbic Acid / Q000494:pharmacology; D005260:Female; D007980:Levodopa / Q000031:analogs & derivatives / Q000494:pharmacology; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation
D007980:Levodopa; D008315:Malondialdehyde; C035420:levodopa methyl ester; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid