Inhibition of cell growth and induction of apoptosis in ovarian carcinoma cell lines CaOV3 and SKOV3 by natural withanolide Withaferin A.

Inhibition of cell growth and induction of apoptosis in ovarian carcinoma cell lines CaOV3 and SKOV3 by natural withanolide Withaferin A.
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DOI:
10.1016/j.ygyno.2011.11.044
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发表时间:
2012-03
影响因子:
4.7
通讯作者:
Cohen MS
Cohen MS
中科院分区:
医学2区
文献类型:
--
作者:
Zhang X;Samadi AK;Roby KF;Timmermann B;Cohen MS

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Withaferin A是一种天然的withanterine,在包括乳腺癌在内的各种癌症中显示出抗癌特性,但其在卵巢癌中的作用尚未探索。Notch 1和Notch 3与卵巢癌进展密切相关。我们决定研究Withaferin A在卵巢癌细胞系中的作用及其分子作用机制,包括其对Notch的调节。采用MTS法、克隆形成法、Annexin V/PI流式细胞术和细胞周期分析法检测Withaferin A对卵巢癌细胞系CaOV 3和SKOV 3的作用。进行Western分析以检查作用的分子机制。Withaferin A通过诱导细胞凋亡和细胞周期阻滞抑制CaOV 3和SKOV 3细胞的生长和集落形成。这些变化与Notch 1、Notch 3、cdc 25 C、总Akt和磷酸化Akt以及bcl-2蛋白的下调相关。Withaferin A至少部分通过靶向Notch 1和Notch 3抑制CaOV 3和SKOV 3卵巢癌细胞生长。
Withaferin A, a natural withanolide, has shown anti-cancer properties in various cancers including breast cancer, but its effects in ovarian cancer remain unexplored. Notch 1 and Notch3 are critically involved in ovarian cancer progression. We decided to examine the effects of Withaferin A in ovarian carcinoma cell lines and its molecular mechanism of action including its regulation of Notch. The effects of Withaferin A were examined in CaOV3 and SKOV3 ovarian carcinoma cell lines using MTS assay, clonogenic assay, annexin V/propidium iodide flow cytometry, and cell cycle analysis. Western analysis was conducted to examine the molecular mechanisms of action. Withaferin A inhibited the growth and colony formation of CaOV3 and SKOV3 cells by inducing apoptosis and cell cycle arrest. These changes correlated with down-regulation of Notch1, Notch3, cdc25C, total and phosphorylated Akt, and bcl-2 proteins. Withaferin A inhibits CaOV3 and SKOV3 ovarian carcinoma cell growth, at least in part by targeting Notch1 and Notch3.
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