Down-regulation of Notch-1 is associated with Akt and FoxM1 in inducing cell growth inhibition and apoptosis in prostate cancer cells.
Down-regulation of Notch-1 is associated with Akt and FoxM1 in inducing cell growth inhibition and apoptosis in prostate cancer cells.
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DOI：
10.1002/jcb.22770
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发表时间：
2011-01
影响因子：
4
通讯作者：
Sarkar, Fazlul H.
中科院分区：
文献类型：
--
作者：
Wang, Zhiwei;Li, Yiwei;Ahmad, Aamir;Banerjee, Sanjeev;Azmi, Asfar S.;Kong, Dejuan;Wojewoda, Christine;Miele, Lucio;Sarkar, Fazlul H.
尽管已经进行了许多研究以揭示Notch-1的下调对多种人类恶性肿瘤发挥其抗肿瘤活性的机制，但精确的分子机制仍不清楚。在本研究中，我们研究了Notch-1下调的细胞后果，并评估了Notch-1介导的下游靶点改变对前列腺癌（PCa）细胞活力和凋亡的分子后果。我们发现Notch-1的下调导致细胞生长抑制和凋亡诱导，这与Akt和FoxM 1的下调机制相关，首次表明Akt和FoxM 1是Notch-1信号转导的下游靶点。此外，我们发现最初从大豆中发现的“天然试剂”（染料木黄酮）可导致细胞活力显著降低并诱导PCa细胞凋亡，这与Notch-1、Akt和FoxM 1的下调一致。这些结果表明，通过新的药物下调Notch-1可能成为预防肿瘤进展和/或治疗的新方法，这可能是通过PCa中Akt和FoxM 1信号通路的失活介导的。
Although many studies have been done to uncover the mechanisms by which down-regulation of Notch-1 exerts its anti-tumor activity against a variety of human malignancies, the precise molecular mechanisms remain unclear. In the present study, we investigated the cellular consequence of Notch-1 down-regulation and also assessed the molecular consequence of Notch-1-mediated alterations of its downstream targets on cell viability and apoptosis in prostate cancer (PCa) cells. We found that the down-regulation of Notch-1 led to the inhibition of cell growth and induction of apoptosis, which was mechanistically linked with down-regulation of Akt and FoxM1, suggesting for the first time that Akt and FoxM1 are downstream targets of Notch-1 signaling. Moreover, we found that a “natural agent” (genistein) originally discovered from soybean could cause significant reduction in cell viability and induced apoptosis of PCa cells, which was consistent with down-regulation of Notch-1, Akt, and FoxM1. These results suggest that down-regulation of Notch-1 by novel agents could become a newer approach for the prevention of tumor progression and/or treatment, which is likely to be mediated via inactivation of Akt and FoxM1 signaling pathways in PCa.
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新的潜在抗癌药物与前列腺癌协同和ABT-737协同作用。
DOI：
10.1002/pros.21116
发表时间：
2010-06-01
期刊：
The Prostate
影响因子：
--
作者：
Pandit B;Gartel AL
通讯作者：
Gartel AL
影响因子：
3.8
作者：
Bektas, Nuran;ten Haaf, Anette;Veeck, Juergen;Wild, Peter Johannes;Luescher-Firzlaff, Juliane;Hartmann, Arndt;Knuechel, Ruth;Dahl, Edgar
通讯作者：
Dahl, Edgar
影响因子：
11.2
作者：
Li, Yiwei;Kucuk, Omer;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
影响因子：
3.8
作者：
Chandran, Uma R.;Ma, Changqing;Dhir, Rajiv;Bisceglia, Michelle;Lyons-Weiler, Maureen;Liang, Wenjing;Michalopoulos, George;Becich, Michael;Monzon, Federico A.
通讯作者：
Monzon, Federico A.
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.