Evidence for cytostatic effect of cyclophosphamide on human vein endothelial cells in cancer therapy: Preliminary in vitro results

In cancer therapy, a number of drugs with different mechanisms of action are in clinical use, which act directly after administration without metabolism, while others only become active in the metabolites produced in the liver. Such drugs/metabolites - especially when administered parenterally - interact in high concentrations with the endothelium. Whether this induces adverse responses of the endothelial cells (EC) is barely studied for many medicaments. This pilot in vitro study revealed that the addition of cyclophosphamide (CPA) to the culture medium (5 or 10 mM, respectively) showed a clear influence on EC compared to non-treated EC: The number of adherent human vein endothelial cells (HUVEC) decreased by the addition of CPA in a concentration-dependent manner compared to the untreated control, whereby the vitality of adherent cells was not affected. In addition, concomitant with activation of the adherent HUVEC, increased migratory activity occurred. These results are in agreement with clinical events like thromboses in patients in compromised condition under therapy with CPA, as the detachment of EC might induce responses of circulating platelets leading to the adherence and aggregation with the risk of the formation of thrombi. Whether CPA acts directly or via toxic metabolites on EC will be examined in more detail in following studies.