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Mitotic catastrophe and apoptosis induced by docetaxel in hormone‐refractory prostate cancer cells
Author(s) -
Fabbri Francesco,
Amadori Dino,
Carloni Silvia,
Brigliadori Giovanni,
Tesei Anna,
Ulivi Paola,
Rosetti Marco,
Vannini Ivan,
Arienti Chiara,
Zoli Wainer,
Silvestrini Rosella
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21522
Subject(s) - mitotic catastrophe , apoptosis , mitosis , programmed cell death , docetaxel , prostate cancer , cancer research , cell cycle , caspase , cancer cell , intrinsic apoptosis , necrosis , microbiology and biotechnology , biology , chemistry , cancer , medicine , biochemistry
Studies performed in different experimental and clinical settings have shown that Docetaxel (Doc) is effective in a wide range of tumors and that it exerts its activity through multiple mechanisms of action. However, the sequence of events induced by Doc which leads to cell death is still not fully understood. Moreover, it is not completely clear how Doc induces mitotic catastrophe and whether this process is an end event or followed by apoptosis or necrosis. We investigated the mechanisms by which Doc triggers cell death in hormone‐refractory prostate cancer cells by analyzing cell cycle perturbations, apoptosis‐related marker expression, and morphologic cell alterations. Doc induced a transient increase in G2/M phase followed by the appearance of G0/1 hypo‐ and hyperdiploid cells and increased p21 expression. Time‐ and concentration‐dependent apoptosis was induced in up to 70% of cells, in concomitance with Bcl‐2 phosphorylation, which was followed by caspase‐2 and ‐3 activation. In conclusion, Doc would seem to trigger apoptosis in hormone‐refractory prostate cancer cells via mitotic catastrophe through two forms of mitotic exit, in concomitance with increased p21 expression and caspase‐2 activation. J. Cell. Physiol. 217: 494–501, 2008. © 2008 Wiley‐Liss, Inc.