Effects of Sodium Warfarin and Sodium Heparin Plus Anticancer Agents on Growth of Rat C6 Glioma Cells2

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Abstract
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 10−5M), but both cell growth and cellular adherence to culture plates were inhibited at high doses (10−3 to 10−2M). Sodium heparin, even at high doses, did not affect cell growth or adherence. Warfarin (10−3M) 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 (10−3M) or heparin (12.6 U/ml) pretreatment plus a 2-hour incubation with one of seven anticancer agents. Supraadditive toxic effects were produced by warfarin plus chlorambucil, heparin plus chlorambucil, heparin plus carmustine, and heparin plus teniposide. At low doses of warfarin (10−5M) or heparin (0.126 U/ml), heparin plus carmustine and heparin plus teniposide remained synergistic.