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-responsiv e LNCaP and androgen independent DU145 prostate cancer cell lines. Cells we re treated for 48 and 72 h with 0.05-1 nM of the synthetic androgen R1881 a nd with 100 nM taxol. Treatment of LNCaP cells with 0.05 nM R1881 led to in creased cell proliferation, whereas treatment with 1 nM R1881 resulted in i nhibit-ed cell division, DNA cycle arrest, and altered centrosome organizat ion. After treatment with 1 nM R1881, chromatin became clustered, nuclear e nvelopes convoluted, and mitochondria accumulated around the nucleus. Immun ofluorescence microscopy with antibodies to centrosomes showed altered cent rosome structure. Although centrosomes were closely associated with the nuc leus in untreated cells, they dispersed into the cytoplasm after treatment with 1 nM R1881. Microtubules were only faintly detected in 1 nM R1881-trea ted LNCaP cells. The effects of taxol included microtubule bundling and alt ered mitochondria morphology, but not DNA organization. As expected, the an drogen-independent prostate cancer cell line DU145 was not affected by R188 1. Treatment with taxol resulted in bundling of microtubules in both cell l ines. Additional taxol effects were seen in DU145 cells with micronucleatio n of DNA, an indication of apoptosis. Simultaneous treatment with R1881 and taxol had no additional effects on LNCaP or DU145 cells. These results sug gest that LNCaP and DU145 prostate cancer cells show differences not only i n androgen responsiveness but in sensitivity to taxol as well. (C) 2000 Wil ey-Liss, inc.