Centrosome impairments and consequent cytokinesis defects are possible mechanisms of taxane drugs.
Taxol and taxotere are two of the most promising anticancer drugs. To determine the mechanisms responsible for cell death after exposure to low doses of taxane, PC3 cells were treated with taxol and taxotere, and observed with immunofluoroscence microscopy. Pericentriolar material dissociation and blockage of normal centrosome separation were found to result in two different abnormal spindle types; multipolar and monopolar spindles, respectively. The majority of abnormal spindles induced by taxol were monopolar spindles, whereas taxotere mostly induced abnormal multipolar spindles. Consequently, monopolar spindle mitosis resulted in cleavage failure, while multipolar spindle mitosis led to the formation of both cleavage failure and multipolar cell division. Multinucleation characterized interphase cells which had undergone cytokinesis defects. These cells subsequently became giant multinucleated cells after several rounds of cell cycle with sustained cleavage failure, and were gradually eliminated through cell death.
Zhu
Jun
J
Radiobiology Laboratory, California Pacific Medical Center Research Institute, San Francisco, CA 94118, USA.
Beattie
Eric C
EC
Yang
Yang
Y
Wang
Hui-Juan
HJ
Seo
Jae-Young
JY
Yang
Li-Xi
LX
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D018385:Centrosome / Q000187:drug effects*; D048749:Cytokinesis / Q000187:drug effects; D000077143:Docetaxel; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D008941:Spindle Apparatus / Q000187:drug effects; D043823:Taxoids / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel