新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » BIOON报道 » ACS Chem. Biol.:以癌细胞线粒体为靶标克服癌细胞耐药性问题

ACS Chem. Biol.:以癌细胞线粒体为靶标克服癌细胞耐药性问题

来源:生物谷 2013-05-23 16:35

2013年5月23日讯 /生物谷BIOON/--近期发表在ACS Chemical Biology上的文章称,改造抗癌药物直指癌细胞的能量工厂或能够防止癌细胞的抗药性。

该文章的通讯作者Shana Kelley博士解释道doxorubicin和其他类型的化疗药物的工作机制是破坏癌细胞核内的基因。因为癌细胞分裂速度比正常细胞快,药物就能够破坏癌细胞。但是癌细胞会出现药物抗性,进化出能够将药物泵出细胞核的结构。Kelley博士研究组希望将doxorubicin转移入线粒体,破坏线粒体基因也可以杀死癌细胞。

研究人员将doxorubicin与多肽结合改造了该药物,使其靶标为线粒体而不是细胞核。发现该药物能够有效杀死癌细胞,即使癌细胞已经有泵出药物的结构。研究人员推测该技术或许对所有的细胞核靶向的抗癌药物都适用。(生物谷Bioon.com)

Targeted Delivery of Doxorubicin to Mitochondria

Graham R. Chamberlain, David V. Tulumello, Shana O. Kelley

Several families of highly effective anticancer drugs are selectively toxic to cancer cells because they disrupt nucleic acid synthesis in the nucleus. Much less is known, however, about whether interfering with nucleic acid synthesis in the mitochondria would have significant cellular effects. In this study, we explore this with a mitochondrially targeted form of the anticancer drug doxorubicin, which inhibits DNA topoisomerase II, an enzyme that is both in mitochondria and nuclei of human cells. When doxorubicin is attached to a peptide that targets mitochondria, it exhibits significant toxicity. However, when challenged with a cell line that overexpresses a common efflux pump, it does not exhibit the reduced activity of the nuclear-localized parent drug and resists being removed from the cell. These results indicate that targeting drugs to the mitochondria provides a means to limit drug efflux and provide evidence that a mitochondrially targeted DNA topoisomerase poison is active within the organelle.

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库