Decrease in prostate specific antigen secretion correlated with docetaxel-induced growth inhibition and apoptosis in human prostate tumor cells.
The antitumor activity of docetaxel in human prostate tumor cells and correlation between cell-growth inhibition and prostate specific antigen (PSA) secretion were investigated. Cultured human prostate tumor cell lines (LNCaP, DU1 45 and PC-3) were treated with test drugs,after which the number of viable cells and PSA levels in the medium were determined. Apoptosis was assessed by changes in chromatin structure, DNA fragmentation, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) and Annexin V assay. Docetaxel inhibited cell proliferation in a dose-dependent fashion in all cell lines,with IC50 levels from 0.90 to 4.2 nM,which were similar to those of paclitaxel,but more potent than mitoxantrone,estramustine,or cisplatin. Docetaxel-treated cells underwent cell-cycle arrest in the G2/M phase and apoptosis as indicated by chromatin condensation and DNA fragmentation. In docetaxel-treated LNCaP cells,there was a linear correlation between growth inhibition and the decline in PSA level in the culture medium. It was demonstrated that docetaxel had potent antitumor activity against human prostate tumor cells,and the decrease in cell growth was associated with a decrease in PSA secretion,suggesting that PSA would be a useful biological marker for monitoring the efficacy of docetaxel in a clinical setting.
Noguchi
Keiko
K
Drug Safety Evaluation, Preclinical Development, R & D, sanofi-aventis K. K.
Shakuto
Shuji
S
Sakairi
Takashi
T
Yoshida
Yasushi
Y
D017304:Annexin A5 / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure; D053938:DNA Fragmentation / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000473:pathology*; D043823:Taxoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D017304:Annexin A5; D000970:Antineoplastic Agents; D015415:Biomarkers; D002843:Chromatin; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen