Solanine induces mitochondria-mediated apoptosis in human pancreatic cancer cells.

Solanine induces mitochondria-mediated apoptosis in human pancreatic cancer cells.
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茄碱诱导人胰腺癌细胞线粒体介导的细胞凋亡

DOI:
10.1155/2014/805926
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发表时间:
2014
影响因子:
--
通讯作者:
Zhou M
Zhou M
中科院分区:
生物学3区
文献类型:
--
作者:
Sun H;Lv C;Yang L;Wang Y;Zhang Q;Yu S;Kong H;Wang M;Xie J;Zhang C;Zhou M

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甾体生物碱已被认为是潜在的抗癌化合物。然而,类固醇生物碱如何抑制肿瘤生长的潜在机制在很大程度上是未知的。在此,我们报道了龙葵碱,一种甾体生物碱的物质,在体外和体内对胰腺癌细胞生长的抑制具有积极的作用。在胰腺癌细胞和nu/nu裸鼠模型中,我们发现龙葵碱通过caspase-3依赖的线粒体凋亡抑制癌细胞生长。在机械上,龙葵碱通过下调Bcl-2/Bax比率促进线粒体膜通透性转换孔(MPTP)的开放;此后,细胞色素c和Smac从线粒体释放到细胞质中以将半胱天冬酶-3酶原加工成活化形式。此外,我们发现在龙葵碱处理的细胞中,肿瘤转移相关蛋白MMP-2和MMP-9的表达也降低。因此,我们的研究结果表明龙葵碱是一种有效的化合物,用于治疗胰腺癌。
Steroid alkaloids have been suggested as potential anticancer compounds. However, the underlying mechanisms of how steroid alkaloids inhibit the tumor growth are largely unknown. Here, we reported that solanine, a substance of steroid alkaloids, has a positive effect on the inhibition of pancreatic cancer cell growth in vitro and in vivo. In pancreatic cancer cells and nu/nu nude mice model, we found that solanine inhibited cancer cells growth through caspase-3 dependent mitochondrial apoptosis. Mechanically, solanine promotes the opening of mitochondrial membrane permeability transition pore (MPTP) by downregulating the Bcl-2/Bax ratio; thereafter, Cytochrome c and Smac are released from mitochondria into cytosol to process the caspase-3 zymogen into an activated form. Moreover, we found that the expression of tumor metastasis related proteins, MMP-2 and MMP-9, was also decreased in the cells treated with solanine. Therefore, our results suggested that solanine was an effective compound for the treatment of pancreatic cancer.
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