Modulation of cell-cycle regulatory signaling network by 2-methoxyestradiol in prostate cancer cells is mediated through multiple signal transduction pathways

Biochemistry
Gibanananda RaySushanta K Banerjee

Abstract

2-Methoxyestradiol (2-ME(2)), a promising anticancer drug, induces growth arrest and apoptosis in 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-ME(2) on the cell division cycle of prostate cancer cells. Chronic exposure of high doses of 2-ME(2) enhance the accumulation of cells in S and G2/M phases, while cell numbers in the G1 phase were reduced significantly by this treatment. Because cyclin B1 overexpression, induction of cdc2 phosphorylation, and its regulatory proteins wee1 and phospho-cdc25C (interphase and mitotic forms) by 2-ME(2) 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 cdc2 phosphorylation and its upstream regulatory molecular networks may be associated with the ultimate impacts of 2-ME(2). Because phosphorylation of cdc2 and upregulation of wee1 by 2-ME(2) can be abolished by both extracellular receptor kinase (ERK) inhibitor (U0126) and c-Jun N-terminal kinase (JNK) inhibitor (SP600125), our studies indicate that the 2-ME(2)-induced upregulation of wee1 and subsequent cdc2 phosphorylation ...Continue Reading

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Citations

Jan 1, 2008·Acta Crystallographica. Section E, Structure Reports Online·Hao JiangQian Zhang
May 30, 2008·Cell Biochemistry and Function·Catherina Van ZijlAnnie Joubert
Oct 16, 2007·International Journal of Cancer. Journal International Du Cancer·Peter J Van VeldhuizenSushanta K Banerjee
Jun 4, 2008·Molecular Carcinogenesis·Masayuki Fukui, Bao Ting Zhu
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Oct 2, 2012·Molecular Medicine Reports·Sheyu LinLin He
Jan 5, 2013·Molecular Cancer Therapeutics·Suman KambhampatiSushanta K Banerjee

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