Apoptosis of androgen-independent mammary and prostate cell lines induced by topoisomerase inhibitors: common pathway of gene regulation.
New treatments for hormone-independent tumor are urgently needed since androgen-dependent cancer cells eventually progress to -independent cells after hormonal manipulation. In the present study, etoposide and camptothecin were used to induce proliferation-dependent death of these cells. Each of the agents, at the doses used, induces the apoptosis of AT-3, CS 2, and TSU-pr1 cells based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability. Northern blot analysis was used to identify a series of genes whose expression is enhanced during the apoptotic pathway. During the apoptotic process induced by the agents, expression of cyclin-dependent kinase inhibitor p27 increased. Flow cytometric analysis showed that the treatment resulted in a block in G2/M of the cell cycle. These results demonstrate that these cells retain the ability to undergo apoptosis by etoposide and camptothecin, and cyclin-dependent kinase inhibitor plays some role during apoptotic pathway.
Furuya
Y
Y
Department of Urology, School of Medicine, Chiba University, Japan.
Ohta
S
S
Ito
H
H
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins; D002470:Cell Survival / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005047:Etoposide / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D011471:Prostatic Neoplasms; D051381:Rats; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D000728:Androgens; C493961:Cdkn1b protein, mouse; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005047:Etoposide; D018844:Cyclin-Dependent Kinases; D002166:Camptothecin