Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 494-501 |
| Number of pages | 8 |
| Journal | Journal of Cellular Physiology |
| Volume | 217 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Nov 2008 |
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ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology
- Physiology
Cite this
Mitotic catastrophe and apoptosis induced by docetaxel in hormone-refractory prostate cancer cells. / Fabbri, Francesco; Amadori, Dino; Carloni, Silvia; Brigliadori, Giovanni; Tesei, Anna; Ulivi, Paola; Rosetti, Marco; Vannini, Ivan; Arienti, Chiara; Zoli, Wainer; Silvestrini, Rosella.
In: Journal of Cellular Physiology, Vol. 217, No. 2, 11.2008, p. 494-501.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mitotic catastrophe and apoptosis induced by docetaxel in hormone-refractory prostate cancer cells
AU - Fabbri, Francesco
AU - Amadori, Dino
AU - Carloni, Silvia
AU - Brigliadori, Giovanni
AU - Tesei, Anna
AU - Ulivi, Paola
AU - Rosetti, Marco
AU - Vannini, Ivan
AU - Arienti, Chiara
AU - Zoli, Wainer
AU - Silvestrini, Rosella
PY - 2008/11
Y1 - 2008/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=51449083767&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=51449083767&partnerID=8YFLogxK
U2 - 10.1002/jcp.21522
DO - 10.1002/jcp.21522
M3 - Article
C2 - 18615564
AN - SCOPUS:51449083767
VL - 217
SP - 494
EP - 501
JO - Journal of cellular and comparative physiology
JF - Journal of cellular and comparative physiology
SN - 0021-9541
IS - 2
ER -