EFFECTS OF ALPHA-DIFLUOROMETHYLORNITHINE AND 5-FLUOROURACIL ON THE PROLIFERATION OF A HUMAN-COLON ADENOCARCINOMA CELL-LINE

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (9) , 4035-4038
Abstract
The effectiveness of .alpha.-difluoromethylornithine (DFMO) against a human colon adenocarcinoma cell line (Colo-205) was tested alone and in combination with 5-fluorouracil (5-FU). DFMO (2 .times. 10-4 M) and 5-FU (10-6 M) inhibited Colo-205 cell proliferation. ABove 5 .times. 10-4 M DFMO (P < 0.001) and at 10-4 M 5-FU (P < 0.001), Colo 205 growth was completely inhibited. Although DFMO did not sensitize Colo-205 cells to a noninhibitory concentration of 5-FU, the effectiveness of inhibitory concentrations of 5-FU and DFMO in reducing Colo-205 cell growth was additive. DFMO (2 .times. 10-4 M) caused 89-93% inhibition of ornithine decarboxylase activity (P < 0.001) and reduced levels of putrescine (93%; P < 0.01) and spermidine (57%; P < 0.02). Growth rate and the intracellular putrescine and spermidine contents were restored by 10-6 M putrescine. DFMO could be an effective chemotherapeutic agent against human colonic cancer because of its effects at such unusually low concentrations in vitro.