Inhibition of adhesion breast cancer cells by anticoagulant drugs and cimetidine.

Recent studies suggest that anticoagulant drugs and cimetidine therapy in malignancy may improve cancer survival and inhibit the metastatic process. In this study we investigated and compared the effects of anticoagulant drugs (unfractionated heparin, warfarin, acetylsalicylic acid, low-molecular-weight heparins--nandroparinum, enoxaparinum, dalteparinum and reviparinum), cimetidine and combination of cimetidine with anticoagulants on adhesion of highly invasive breast cancer cells lines - BT 549 and MDA-MB-231 (MDA 231)--in vitro. High antiadhesion effect was observed with cimetidine, warfarin and acetylsalicylic acid. Low-molecular-weight heparins had a small antiadhesion effect in independent use. In combination with cimetidine, a potential effect of cimetidine on the antiadhesion was observed. The antiadhesion effect was dependent on the type of the cancer cell line. Different effects between cell lines BT 549 and MDA 231 were observed. The strongest antiadhesion effect was obtained using the combination of cimetidine with acetylsalicylic acid. In the majority of applications of the drugs and their combinations, a proportional antiadhesion effect was dependent on the concentration and time. We suppose that anticoagulant drugs might have higher antimetastatic effect in combination with cimetidine. The choice of anticoagulants can decrease the adhesion, decrease tumor angiogenesis and cause the shortening of blood clotting time. Cimetidine can decrease the adhesion of cancer cells and increase the activity of NK cells. Indeed, according to our results, application of cimetidine and anticoagulant drugs intensifies the antiadhesion effect together with other antimetastatic effects.