Doxazosin-induced clusterin expression and apoptosis in prostate cancer cells.
The purpose of this study was to correlate temporal expression of clusterin and apoptosis in androgen-independent human prostate cancer cells (PC-3) treated with 25 microM doxazosin. DNA fragmentation, reverse transcriptase polymerase chain reaction, and terminal transferase-mediated biotinylated 16-desoxy-uridene triphosphate nick-end labeling (TUNEL) assays were used to assess degree of apoptosis and temporal and spatial expression of clusterin mRNA and protein. DNA fragmentation was significant at 48 hours. Clusterin mRNA expression was 3-fold higher than control at 9 hours and was maintained over 48 hours. The TUNEL assay showed increasing percentage of apoptotic cells and presence of clusterin after doxazosin treatment. During doxazosin-induced apoptosis in PC3 cells, clusterin appeared to initially accumulate in the cytoplasm and protect against apoptosis; later, after its transport to the nucleus, clusterin was no longer able to suppress apoptosis.
Youm
Yun Hee
YH
Life Science Institute, Eulji University School of Medicine, Seoul, South Korea.
Yang
Hyunwon
H
Yoon
Yong-Dal
YD
Kim
Duk-Yoon
DY
Lee
Chung
C
Yoo
Tag Keun
TK
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D051152:Clusterin / Q000187:drug effects* / Q000378:metabolism; D017292:Doxazosin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D051152:Clusterin; D012333:RNA, Messenger; D017292:Doxazosin