Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells.
Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells.
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DOI：
10.1016/j.bbamcr.2011.05.003
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Eibl G
中科院分区：
文献类型：
--
作者：
Takahashi H;Chen MC;Pham H;Angst E;King JC;Park J;Brovman EY;Ishiguro H;Harris DM;Reber HA;Hines OJ;Gukovskaya AS;Go VL;Eibl G
黄芩（SB）和SB衍生的多酚在包括胰腺癌（PaCa）在内的多种癌症中具有抗增殖活性。然而，精确的分子机制尚未完全确定。SB提取物和SB衍生的多酚（汉黄芩素，黄芩苷，黄芩素）被用来确定其抗增殖机制。黄芩素以剂量依赖性方式显著抑制PaCa细胞系的增殖，而汉黄芩素和黄芩苷表现出不太稳健的效果。黄芩素处理诱导细胞凋亡，细胞色素c从线粒体释放，caspase-3和-7和PARP活化。一般的半胱天冬酶抑制剂zVAD-fastrin逆转黄芩苷诱导的细胞凋亡，表明半胱天冬酶依赖的机制。黄芩素可能通过转录机制降低Bcl-2蛋白家族的抗凋亡成员Mcl-1的表达。基因敲低Mcl-1导致细胞凋亡的显著诱导。黄芩素对细胞凋亡的影响被Mcl-1过表达显著减弱，表明Mcl-1在此过程中起关键作用。我们的研究结果提供了黄芩素通过下调抗凋亡Mcl-1蛋白诱导胰腺癌细胞凋亡的证据。
Scutellaria baicalensis (SB) and SB-derived polyphenols possess anti-proliferative activities in several cancers, including pancreatic cancer (PaCa). However, the precise molecular mechanisms have not been fully defined. SB extract and SB-derived polyphenols (wogonin, baicalin, and baicalein) were used to determine their anti-proliferative mechanisms. Baicalein significantly inhibited the proliferation of PaCa cell lines in a dose-dependent manner, whereas wogonin and baicalin exhibited a much less robust effect. Treatment with baicalein induced apoptosis with release of cytochrome c from mitochondria, and activation of caspase-3 and -7 and PARP. The general caspase inhibitor zVAD-fmk reversed baicalein-induced apoptosis, indicating a caspase-dependent mechanism. Baicalein decreased expression of Mcl-1, an anti-apoptotic member of the Bcl-2 protein family, presumably through a transcriptional mechanism. Genetic knockdown of Mcl-1 resulted in marked induction of apoptosis. The effect of baicalein on apoptosis was significantly attenuated by Mcl-1 over-expression, suggesting a critical role of Mcl-1 in this process. Our results provide evidence that baicalein induces apoptosis in pancreatic cancer cells through down-regulation of the anti-apoptotic Mcl-1 protein.
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影响因子：
3.8
作者：
Schulze-Bergkamen H;Fleischer B;Schuchmann M;Weber A;Weinmann A;Krammer PH;Galle PR
通讯作者：
Galle PR
影响因子：
2.9
作者：
Eibl, G;Reber, HA;Hines, OJ
通讯作者：
Hines, OJ
影响因子：
2.9
作者：
Funahashi, Hitoshi;Satake, Makoto;Eibl, Guido
通讯作者：
Eibl, Guido
影响因子：
2.4
作者：
Kim, Eun Ji;Park, Heesook;Park, Jung Han Yoon
通讯作者：
Park, Jung Han Yoon
影响因子：
3.6
作者：
Chen, Wenjie;Bai, Lang;Lin, Yong
通讯作者：
Lin, Yong