Effects of Sodium Warfarin and Sodium Heparin Plus Anticancer Agents on Growth of Rat C6 Glioma Cells

: The effects of racemic sodium warfarin (warfarin) and sodium heparin (heparin) on brain tumor cells were assessed in the rat C6 glioma cell line. After anticoagulant treatment lasting up to 5 days, cell growth was not inhibited by warfarin at low doses (10(-4) to 10(-5) M), but both cell growth and cellular adherence to culture plates were inhibited at high doses (10(-3) to 10(-2) M). Sodium heparin, even at high doses, did not affect cell growth or adherence. Warfarin (10(-3) M) significantly decreased and heparin (12.6 U/ml) had no effect on [3H]thymidine and [14C]leucine incorporation after 3- or 24-hour anticoagulant treatment. Colony formation studies examined the effects of 24-hour warfarin (10(-3) M) or heparin (12.6 U/ml) pretreatment plus a 2-hour incubation with one of seven anticancer agents. Supra-additive toxic effects were produced by warfarin plus chlorambucil, heparin plus chlorambucil, heparin plus carmustine, and heparin plus teniposide. At low doses of warfarin (10(-5) M) or heparin (0.126 U/ml), heparin plus carmustine and heparin plus teniposide remained synergistic.