Withaferin A, a steroidal lactone from Withania somnifera, induces mitotic catastrophe and growth arrest in prostate cancer cells.
Withaferin A, a steroidal lactone from Withania somnifera, induces mitotic catastrophe and growth arrest in prostate cancer cells.
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DOI：
10.1021/np400441f
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发表时间：
2013-10-25
影响因子：
5.1
通讯作者：
Damodaran C
中科院分区：
文献类型：
--
作者：
Roy RV;Suman S;Das TP;Luevano JE;Damodaran C
细胞周期失调与前列腺癌（CaP）的发病机制密切相关。针对G0/G1或G2/M期抑制包括CaP在内的癌症生长的细胞周期调节剂的临床试验正在增加。在这项研究中，我们确定了草药分子Withaferin-A （WA）对CaP细胞的细胞周期调控潜力。WA在两种CaP细胞系（PC3和DU145）中诱导不可逆的G2/M阻滞48小时。G2/M阻滞伴随着磷酸化Wee1、磷酸化组蛋白H3、p21和Aurora-B的上调。另一方面，在wa处理的CaP细胞中，细胞周期蛋白（E2， A, B1）和磷酸化Cdc2 （Tyr15）下调。此外，在wa处理的CaP细胞中，磷酸化的Chk1 （Ser345）和Chk2 （Thr68）水平明显降低。我们的研究结果表明，Cdc2的激活导致m期积累，伴有异常复制，并引发有丝分裂灾难，导致细胞死亡。总之，这些结果清楚地强调了WA作为细胞周期G2/M期调节剂和CaP治疗剂的潜力。
Cell cycle deregulation is strongly associated with the pathogenesis of prostate cancer (CaP). Clinical trials of cell cycle regulators that target either the G0/G1 or G2/M phase to inhibit the growth of cancers including CaP are increasing. In this study, we determined the cell-cycle regulatory potential of the herbal molecule Withaferin-A (WA) on CaP cells. WA induced irreversible G2/M arrest in both CaP cell lines (PC3 and DU145) for 48 h. The G2/M arrest was accompanied by upregulation of phosphorylated Wee1, phophorylated histone H3, p21 and Aurora-B. On the other hand, downregulation of cyclins (E2, A, and B1) and phorphorylated Cdc2 (Tyr15) was observed in WA-treated CaP cells. In addition, decreased levels of phosphorylated Chk1 (Ser345) and Chk2 (Thr68) were evident in WA-treated CaP cells. Our results suggest that activation of Cdc2 leads to accumulation in M-phase, with abnormal duplication, and initiation of mitotic catastrophe that results in cell death. In conclusion, these results clearly highlight the potential of WA as a regulator of the G2/M phase of the cell cycle and as a therapeutic agent for CaP.
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DOI：
10.1006/bbrc.1996.5933
发表时间：
1997-01-13
影响因子：
3.1
作者：
Honda, R;Ohba, Y;Yasuda, H
通讯作者：
Yasuda, H
DOI：
10.1073/pnas.0609299104
发表时间：
2007-04-24
影响因子：
11.1
作者：
Hallstrom, Taija M. Kiviharju-af;Jaamaa, Sari;Laiho, Marikki
通讯作者：
Laiho, Marikki
影响因子：
7.2
作者：
Oh, Jung Hwa;Lee, Tae-Jin;Kwon, Taeg Kyu
通讯作者：
Kwon, Taeg Kyu
影响因子：
11.4
作者：
Hagting, A;Karlsson, C;Pines, J
通讯作者：
Pines, J
CDC25B与CDC25A合作以诱导有丝分裂，但在激活中心体的细胞周期蛋白B1-CDK1方面具有独特的作用。
影响因子：
7.8
作者：
Lindqvist, Arne;Kallstrom, Helena;Lundgren, Andreas;Barsoum, Emad;Rosenthal, Christina Karlsson
通讯作者：
Rosenthal, Christina Karlsson