| Abstract
| - 2-Methoxyestradiol (2-ME2), a promising anticancer drug, induces growth arrest and apoptosisin various androgen-dependent (LNCaP) and -independent (DU145 and PC-3) prostate cancer cell lines.Moreover, flow cytometric analysis indicated a novel dual impact of 2-ME2 on the cell division cycle ofprostate cancer cells. Chronic exposure of high doses of 2-ME2 enhance the accumulation of cells in Sand G2/M phases, while cell numbers in the G1 phase were reduced significantly by this treatment. Becausecyclin B1 overexpression, induction of cdc2 phosphorylation, and its regulatory proteins wee1 and phospho-cdc25C (interphase and mitotic forms) by 2-ME2 treatment correlated with the induction of apoptosis,growth arrest at the G2/M phase, and accumulation of the S phase, we reasoned that cyclin B1 and cdc2phosphorylation and its upstream regulatory molecular networks may be associated with the ultimateimpacts of 2-ME2. Because phosphorylation of cdc2 and upregulation of wee1 by 2-ME2 can be abolishedby both extracellular receptor kinase (ERK) inhibitor (U0126) and c-Jun N-terminal kinase (JNK) inhibitor(SP600125), our studies indicate that the 2-ME2-induced upregulation of wee1 and subsequent cdc2phosphorylation are mediated through mitogen-activated protein kinase (MAPK)−ERK−JNK signalingpathways.
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