TY - JOUR
T1 - Induction of apoptosis in androgen‐independent human prostate cancer cells undergoing thymineless death
AU - Kyprianou, Natasha
AU - Bains, Arvinder K.
AU - Jacobs, Stephen C.
PY - 1994/8
Y1 - 1994/8
N2 - Previous studies have demonstrated that androgen responsive human prostate cancer cells can be induced to undergo programmed cell death after androgen ablation. By contrast, androgen‐independent human prostate cancer cells do not activate this apoptotic pathway in response to androgen ablation. In the present study, two androgen‐independent human prostatic cell lines, PC‐3 and DU‐145, were used as in vitro model systems to investigate the possibility of induction of programmed cell death in response to non‐androgen ablative cytotoxic drugs. Treatment of these cells with the fluorinated pyrimidines, 5‐fluoro‐2‐deoxyuridine or trifluorothymidine, resulted in a significant decrease in cell viability, over a period of 96 hr of exposure to the drugs, as determined by the trypan blue exclusion assay. The characteristic DNA fragmentation into a nucleosomal ladder and induction of expression of specific apoptosis‐related genes, such as TRPM‐2/SGP‐2, and TGF‐β1, but not the growth‐related genes, c‐myc, c‐fos, and p53, temporally correlated with activation of apoptotic cell death in both systems. Simultaneous treatment with exogenous thymidine completely abrogated the fluoropyrimidine‐induced cytotoxic effect in both cell lines, as well as the nucleosomal fragmentation of DMA, indicating that this apoptotic process is due to the induction of “thymineless” state. These results suggest that androgen‐independent human prostate cancer cells retain the ability to activate the apoptotic cascade, after treatment with cytotoxic drugs that induce a “thymineless” state. © 1994 Wiley‐Liss, Inc.
AB - Previous studies have demonstrated that androgen responsive human prostate cancer cells can be induced to undergo programmed cell death after androgen ablation. By contrast, androgen‐independent human prostate cancer cells do not activate this apoptotic pathway in response to androgen ablation. In the present study, two androgen‐independent human prostatic cell lines, PC‐3 and DU‐145, were used as in vitro model systems to investigate the possibility of induction of programmed cell death in response to non‐androgen ablative cytotoxic drugs. Treatment of these cells with the fluorinated pyrimidines, 5‐fluoro‐2‐deoxyuridine or trifluorothymidine, resulted in a significant decrease in cell viability, over a period of 96 hr of exposure to the drugs, as determined by the trypan blue exclusion assay. The characteristic DNA fragmentation into a nucleosomal ladder and induction of expression of specific apoptosis‐related genes, such as TRPM‐2/SGP‐2, and TGF‐β1, but not the growth‐related genes, c‐myc, c‐fos, and p53, temporally correlated with activation of apoptotic cell death in both systems. Simultaneous treatment with exogenous thymidine completely abrogated the fluoropyrimidine‐induced cytotoxic effect in both cell lines, as well as the nucleosomal fragmentation of DMA, indicating that this apoptotic process is due to the induction of “thymineless” state. These results suggest that androgen‐independent human prostate cancer cells retain the ability to activate the apoptotic cascade, after treatment with cytotoxic drugs that induce a “thymineless” state. © 1994 Wiley‐Liss, Inc.
KW - apoptosis
KW - prostate cancer
KW - “thymineless” death
UR - http://www.scopus.com/inward/record.url?scp=0027936767&partnerID=8YFLogxK
U2 - 10.1002/pros.2990250203
DO - 10.1002/pros.2990250203
M3 - Article
C2 - 8036180
AN - SCOPUS:0027936767
SN - 0270-4137
VL - 25
SP - 66
EP - 75
JO - Prostate
JF - Prostate
IS - 2
ER -