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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.