TY - JOUR
T1 - Induction of apoptosis by cryptophycin 1, a new antimicrotubule agent
AU - Mooberry, Susan L.
AU - Busquets, Lizette
AU - Tien, Georgia
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1997
Y1 - 1997
N2 - The ability of cryptophycin I, a new potent cytotoxic antimicrotubule agent, to initiate apoptosis was studied. Treatment of cells with cryptophycin I (50 pM) rapidly caused morphological changes consistent with the induction of apoptosis. DNA strand breakage and fragmentation of the DNA into oligonucleosome-sized fragments was observed, and this coincided with the loss of cellular DNA. Activation of the cysteine protease CPP32 (caspase 3, YAMA, apopain), a member of the ICE/CED-3-like protease family of apoptosis effectors, was consistent with the execution of cell death by a coordinated sequence of events. Low concentrations of cryptophycin I caused mitotic arrest with the formation of abnormal mitotic spindles without affecting interphase microtubule structures. Unlike other microtubule active agents, cryptophycin-induced mitotic arrest persisted for only a brief period before the onset of apoptosis. There was no evidence of release from G2/M cell cycle arrest. Our results show that low concentrations of cryptophycin I (50 pM) initiated cell death consistent with apoptosis. These data suggest that the cytotoxic effects of cryptophycin I are due in part to its ability to initiate apoptosis rapidly.
AB - The ability of cryptophycin I, a new potent cytotoxic antimicrotubule agent, to initiate apoptosis was studied. Treatment of cells with cryptophycin I (50 pM) rapidly caused morphological changes consistent with the induction of apoptosis. DNA strand breakage and fragmentation of the DNA into oligonucleosome-sized fragments was observed, and this coincided with the loss of cellular DNA. Activation of the cysteine protease CPP32 (caspase 3, YAMA, apopain), a member of the ICE/CED-3-like protease family of apoptosis effectors, was consistent with the execution of cell death by a coordinated sequence of events. Low concentrations of cryptophycin I caused mitotic arrest with the formation of abnormal mitotic spindles without affecting interphase microtubule structures. Unlike other microtubule active agents, cryptophycin-induced mitotic arrest persisted for only a brief period before the onset of apoptosis. There was no evidence of release from G2/M cell cycle arrest. Our results show that low concentrations of cryptophycin I (50 pM) initiated cell death consistent with apoptosis. These data suggest that the cytotoxic effects of cryptophycin I are due in part to its ability to initiate apoptosis rapidly.
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U2 - 10.1002/(SICI)1097-0215(19971104)73:3<440::AID-IJC20>3.0.CO;2-F
DO - 10.1002/(SICI)1097-0215(19971104)73:3<440::AID-IJC20>3.0.CO;2-F
M3 - Article
C2 - 9359493
AN - SCOPUS:0030670103
VL - 73
SP - 440
EP - 448
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 3
ER -