Systemic NF-kappaB activation in blood cells of breast cancer patients.
There is a well-established role for reactive oxygen and nitrogen species, chronic inflammation and immune response in the pathogenesis of breast cancer. Complex interactions between breast cancer cells and surrounding blood vessels are prerequisites for cancer growth and invasion. Reports in the literature concerning the systemic response to, and the effect of, common breast cancer therapy on NF-kappaB and antioxidative defence enzyme expression and activity under clinical conditions are scarce. We determined these parameters in whole blood cell lysate from 16 women with breast cancer before and after combined (cyclophosphamide, doxorubicin, 5-fluorouracil; CAF) therapy and compared the results with 16 healthy women. Significantly higher levels of NF-kappaB and Mn-SOD (both their protein level and their activity) were found in breast cancer patients before and after CAF therapy, in comparison with healthy women. In parallel measurements, no change in the level or activity of catalase (CAT) was detected. According to our findings, it appears that breast cancer creates conditions that increase the level of hydrogen peroxide in the circulating cells and that the applied CAF therapy fails to compensate, therefore creating systemic conditions that favour survival and invasion of breast cancer cells.
VINCA Institute of Nuclear Sciences, 'Sinisa Stanković', Belgrade, Serbia and Montenegro.
Miroslav
M
Adzić
Ana
A
Nićiforović
Vesna
V
Vucić
Zora
Z
Nesković-Konstantinović
Snezana D
SD
Spasić
David R
DR
Jones
Marija B
MB
Radojcić
Mihajlo B
MB
Spasić
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D002374:Catalase / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004789:Enzyme Activation / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D006454:Hemoglobins; D016328:NF-kappa B; D004317:Doxorubicin; D003520:Cyclophosphamide; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005472:Fluorouracil