Androgen and taxol cause cell type-specific alterations of centrosome and DNA organization in androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cells.
We investigated the effects of androgen and taxol on the androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cell lines. Cells were treated for 48 and 72 h with 0.05-1 nM of the synthetic androgen R1881 and with 100 nM taxol. Treatment of LNCaP cells with 0.05 nM R1881 led to increased cell proliferation, whereas treatment with 1 nM R1881 resulted in inhibited cell division, DNA cycle arrest, and altered centrosome organization. After treatment with 1 nM R1881, chromatin became clustered, nuclear envelopes convoluted, and mitochondria accumulated around the nucleus. Immunofluorescence microscopy with antibodies to centrosomes showed altered centrosome structure. Although centrosomes were closely associated with the nucleus in untreated cells, they dispersed into the cytoplasm after treatment with 1 nM R1881. Microtubules were only faintly detected in 1 nM R1881-treated LNCaP cells. The effects of taxol included microtubule bundling and altered mitochondria morphology, but not DNA organization. As expected, the androgen-independent prostate cancer cell line DU145 was not affected by R1881. Treatment with taxol resulted in bundling of microtubules in both cell lines. Additional taxol effects were seen in DU145 cells with micronucleation of DNA, an indication of apoptosis. Simultaneous treatment with R1881 and taxol had no additional effects on LNCaP or DU145 cells. These results suggest that LNCaP and DU145 prostate cancer cells show differences not only in androgen responsiveness but in sensitivity to taxol as well.
Schatten
H
H
Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, Missouri 65211, USA. schattenh@missouri.edu
Ripple
M
M
Balczon
R
R
Weindruch
R
R
Chakrabarti
A
A
Taylor
M
M
Hueser
C N
CN
D000728:Androgens / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D018385:Centrosome / Q000187:drug effects / Q000473:pathology; D004273:DNA, Neoplasm / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D045165:Testosterone Congeners / Q000494:pharmacology
D000728:Androgens; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D045165:Testosterone Congeners; D013196:Dihydrotestosterone; D015741:Metribolone; D017239:Paclitaxel