Vascular endothelium: target or victim of cytostatic therapy?
Chemotherapy continues to be the main therapeutic approach in the treatment of hematological malignancies including acute leukemia. Generally, chemotherapy is used to eliminate cancer cells and to restore normal bone marrow function. Simultaneous action of cytostatic drugs on bone marrow angiogenesis decreases the formation of new capillaries and improves therapeutic effect. However, chemotherapeutic agents may also be cytodestructive for cellular elements of other tissues, particularly the vascular endothelium, which can lead to various cardiovascular complications. In this work, we studied the effects of 2 cytostatic drugs, cytosine arabinoside (ara-C) and daunorubicin (DNR), on cultured human vascular (i.e., umbilical) endothelial cells (ECs). Ara-C and DNR were added to cultured cells at concentrations ranging from 1 ng/mL to 100 microg/mL. Drug effects were studied using phase-contrast microscopy, cell viability tests, BRDU incorporation, immunohistochemistry, flow cytometry, and cell cloning. At various concentrations, ara-C and DNR are able to induce morphological and functional changes in cultured cells related to either cytostatic or cytotoxic action. Moreover, ara-C-treated cultured cells displayed significant disturbances in cell adhesion molecule expression and interaction with blood leukocytes. Preliminary data obtained on acute leukemia patients undergoing standard cytostatic therapy ("7+3" regimen) have shown that concentration of the circulating ECs was significantly increased compared with the control group and could be as high as 500-1500 cells/mL of blood. Results obtained suggest that anticancer chemotherapy may induce systemic damage of vascular endothelium related to massive cell loss and (or) alterations of endothelial function.
Romanov
Yuri A
YA
Laboratory of Human Stem Cells, Institute of Experimental Cardiology, National Cardiology Research Center, 3rd Cherepkovskaya Str. 15-A, Moscow 121552, Russian Federation. romanov@cardio.ru
Chervontseva
Alevtina M
AM
Savchenko
Valery G
VG
Smirnov
Vladimir N
VN
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000166:cytology
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D003561:Cytarabine; D003630:Daunorubicin