Mitotic catastrophe and apoptosis induced by docetaxel in hormone‐refractory prostate cancer cells

Journal of Cellular Physiology - Tập 217 Số 2 - Trang 494-501 - 2008
Francesco� Fabbri1, Dino Amadori1, Silvia Carloni1, Giovanni Brigliadori1, Anna Tesei1, Paola Ulivi1, Marco Rosetti1, Ivan Vannini1, Chiara Arienti1, Wainer Zoli1, Rosella Silvestrini1
1Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola (FC), Italy

Tóm tắt

AbstractStudies 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.

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