Antiproliferative activity of taxol on human tumor and normal breast cells vs. effects on cardiac cells.
The antiproliferative activity of the chemotherapeutic agent taxol was evaluated on 2 normal and 2 carcinoma human breast-cell lines and compared with its effects on newborn rat cardiac cells growing in vitro. Relatively little difference in ID50 response (ranging from 0.6 to 2.0 ng/ml) to taxol was found between normal and tumorous breast epithelial cells. Arrhythmias and slowing of beat frequencies of cardiac cells were induced by taxol but at doses approximately 10 times higher than those necessary to inhibit proliferation in dividing cells. Microtubules assayed by immunostaining appeared to be similarly retracted around the nucleus in both breast and heart cells. Overall, our results suggest that taxol does not selectively inhibit the growth of tumor vs. normal human breast cells. They also support the hypothesis that effects on microtubule integrity are associated with effects on cardiac function and that the clinical cardiac activity of taxol already reported may be due, at least in part, to a direct effect of taxol on cardiac cells as demonstrated in these in vitro studies. Thus, caution is needed, in view of possible cardiac effects, when using taxol in future clinical protocols, especially when combined with other cardioactive agents such as Adriamycin.
Brouty-Boye
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Department of Cell Biology and Anatomy, University of Miami, School of Medicine, FL 33136.
Kolonias
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Lampidis
T J
TJ
D000818:Animals; D001919:Bradycardia / Q000139:chemically induced; D001940:Breast / Q000166:cytology / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D017239:Paclitaxel / Q000627:therapeutic use / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004317:Doxorubicin; D017239:Paclitaxel