Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells.
Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells.
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DOI：
10.1186/s12943-015-0403-4
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发表时间：
2015-07-07
期刊：
影响因子：
37.3
通讯作者：
Panno ML
中科院分区：
文献类型：
--
作者：
De Amicis F;Aquila S;Morelli C;Guido C;Santoro M;Perrotta I;Mauro L;Giordano F;Nigro A;Andò S;Panno ML
五甲氧基补骨脂素（5-甲氧基补骨脂素）是一种天然的补骨脂素衍生物，存在于许多水果和蔬菜中，在多种细胞类型中显示出抗肿瘤作用。在这项研究中，它已经解决了Bergapten如何在乳腺癌细胞诱导自噬过程。在MCF7和ZR-75乳腺癌细胞中，Bergapten通过诱导自噬过程增加Beclin1、PI3KIII、UVRAG、AMBRA的表达以及LC3-I向LC3-II的转化，表现出抗生存反应。LC3-GFP、吖啶橙实验和透射电镜甚至证实了处理后细胞中自噬体的形成增加。bergapten诱导的自噬依赖于PTEN的上调，由于沉默该基因，Beclin1的诱导和p-AKT/p-mTOR信号的下调被逆转。通过使用p38MAPK抑制剂SB203580、NF-Y元件和NF-Y siRNA的定点直接诱变，证实了Bergapten通过p38MAPK/NF-Y参与对PTEN进行转录调控。此外，NF-Y敲低可阻止bergapten诱导的酸性囊泡细胞器积聚（AVOs），加强该元素在介导自噬中的作用。我们的数据表明，PTEN是Bergapten在乳腺癌细胞中诱导自噬的关键靶点。这些发现为Bergapten的作用机制提供了进一步的细节，因此表明植物化学化合物可能在乳腺癌治疗的新策略中实施。本文的在线版本（doi:10.1186/s12943-015- 0404 -4）包含补充材料，仅供授权用户使用。
Bergapten (5-methoxypsoralen), a natural psoralen derivative present in many fruits and vegetables, has shown antitumoral effects in a variety of cell types. In this study, it has been addressed how Bergapten in breast cancer cells induces autophagic process. In MCF7 and ZR-75 breast cancer cells Bergapten exhibited anti-survival response by inducing the autophagic process increasing Beclin1, PI3KIII, UVRAG, AMBRA expression and conversion of LC3-I to LC3-II. LC3-GFP, Acridine orange assay and transmission electron microscopy even confirmed the increased autophagosome formations in treated cells. Bergapten-induced autophagy is dependent by PTEN up-regulation, since silencing this gene, the induction of Beclin1 and the p-AKT/p-mTOR signal down-regulation were reversed. PTEN is transcriptionally regulated by Bergapten through the involvement of p38MAPK/NF-Y, as evidenced by the use of p38MAPK inhibitor SB203580, site-direct mutagenesis of NF-Y element and NF-Y siRNA. Furthermore NF-Y knockdown prevented Bergapten-induced acid vesicular organelle accumulations (AVOs), strengthening the role of this element in mediating autophagy. Our data indicate PTEN as a key target of Bergapten action in breast cancer cells for the induction of autophagy. These findings add further details on the mechanism of action of Bergapten, therefore suggesting that phytochemical compounds may be implemented in the novel strategies for breast cancer treatment. The online version of this article (doi:10.1186/s12943-015-0403-4) contains supplementary material, which is available to authorized users.
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Bergapten通过SMAD4介导的泛素化诱导乳腺癌细胞的ER耗竭。
影响因子：
3.8
作者：
Panno, M. L.;Giordano, F.;Rizza, P.;Pellegrino, M.;Zito, D.;Giordano, C.;Mauro, L.;Catalano, S.;Aquila, S.;Sisci, D.;De Amicis, F.;Vivacqua, A.;Fuqua, S. W. A.;Ando, S.
通讯作者：
Ando, S.
影响因子：
--
作者：
De Amicis, F.;Zupo, S.;Ando, S.
通讯作者：
Ando, S.
影响因子：
5.3
作者：
De Amicis F;Guido C;Santoro M;Lanzino M;Panza S;Avena P;Panno ML;Perrotta I;Aquila S;Andò S
通讯作者：
Andò S
白藜芦醇通过 cAMP 信号通路诱导自噬减轻血管内皮炎症
影响因子：
13.3
作者：
Chen, Ming-liang;Yi, Long;Mi, Man-tian
通讯作者：
Mi, Man-tian
影响因子：
4.7
作者：
Ellington, AA;Berhow, MA;Singletary, KW
通讯作者：
Singletary, KW