Effects of three new folate antagonists on human breast adenocarcinoma cells in vitro and on immune responses in vivo.
The effects of three selected potential folate antagonists on 3H-leucine incorporation of eight established breast adenocarcinoma cell lines were investigated. The compounds studied were 5,8-dideazaisofolic acid, 5-methyl-5,8-dideazaisofolic acid, and 10-oxa-5,8-dideazafolic acid. All three anti-folates were inhibitory to most of the cells tested. 10-Oxa-5,8-dideazafolic acid was more effective in inhibiting the growth of these tumor cell lines. Both natural killer cell activity and phytohemagglutinin (PHA)-induced lymphocyte proliferation were decreased in hamsters injected with these compounds, with 5,8-dideazaisofolic acid being the most potent in this regard. The natural killer cell activity and lymphocyte proliferation returned to normal levels 12 days post-injection of these compounds. These studies suggest that 10-oxa-5,8-dideazafolic acid may be useful for the treatment of human breast tumors.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000970:Antineoplastic Agents; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D013997:Time Factors
D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D008934:Mitogens