Centrosome aberrations after nilotinib and imatinib treatment in vitro are associated with mitotic spindle defects and genetic instability.
Centrosomes play fundamental roles in mitotic spindle organisation, chromosome segregation and maintenance of genetic stability. Recently, we have demonstrated that the tyrosine kinase inhibitor imatinib induces centrosome and chromosome aberrations in vitro. Here, we comparatively investigated the effects of imatinib and the more potent successor drug nilotinib on centrosome, mitotic spindle and karyotype status in primary human fibroblasts. Therapeutic doses of imatinib and/or nilotinib administered separately, consecutively or in combination similarly induced centrosome, mitotic spindle, and karyotype aberrations. Our data suggest that distinct tyrosine kinases likewise targeted by both drugs are essential actuators in maintenance of centrosome and karyotype integrity.
Fabarius
Alice
A
III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany. alice.fabarius@med3.ma.uni-heidelberg.de
Giehl
Michelle
M
Frank
Oliver
O
Spiess
Birgit
B
Zheng
Chun
C
Müller
Martin C
MC
Weiss
Christel
C
Duesberg
Peter
P
Hehlmann
Rüdiger
R
Hochhaus
Andreas
A
Seifarth
Wolfgang
W
D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001549:Benzamides; D002478:Cells, Cultured; D018385:Centrosome / Q000648:ultrastructure*; D043171:Chromosomal Instability; D002869:Chromosome Aberrations / Q000139:chemically induced*; D005347:Fibroblasts / Q000648:ultrastructure; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping; D010879:Piperazines / Q000009:adverse effects*; D011743:Pyrimidines / Q000009:adverse effects*; D012044:Regression Analysis; D008941:Spindle Apparatus / Q000648:ultrastructure*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib