Different docetaxel-induced apoptotic pathways are present in prostate cancer cell lines LNCaP and PC-3.
OBJECTIVE
To investigate the molecular machinery of docetaxel (Taxotere)-initiated death signaling on prostate cancer cell lines LNCaP and PC-3. Taxotere is a member of the taxane family of chemotherapeutic agents. It has been shown to disrupt microtubule dynamics causing mitotic arrest, which leads to cell death. Taxotere has demonstrated induction of cell death in LNCaP and PC-3 cells. However, the pathways by which apoptosis occurs differ in each cell line.


METHODS
The prostate cancer cell lines, LNCaP and PC-3, were treated with 40 nM Taxotere for various lengths of time (0.5 to 24 hours). Western blot analysis was used for protein analysis.


RESULTS
LNCaP cells demonstrated caspase-3 and caspase-7 cleavage, and PC-3 cells demonstrated only caspase-8 and BH3-interacting domain death agonist cleavage. Only LNCaP cells were observed to express clusterin expression; PC-3 cells expressed a novel apoptosis inhibitor, survivin.


CONCLUSIONS
In this study, we demonstrated two distinctly different Taxotere-induced apoptotic pathways in LNCaP and PC-3 cells that may be of clinical importance when treating prostate cancer.
Muenchen
H J
HJ
Department of Internal Medicine (Division of Hematology/Oncology), University of Michigan, Ann Arbor, Michigan, USA.
Poncza
P J
PJ
Pienta
K J
KJ
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D051152:Clusterin; D000077143:Docetaxel; D006023:Glycoproteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones / Q000187:drug effects / Q000378:metabolism; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D000077022:Survivin; D043823:Taxoids; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011506:Proteins; D000077022:Survivin; D043823:Taxoids; D000077143:Docetaxel; D020169:Caspases; D017239:Paclitaxel