Tetrandrine is a potent cell autophagy agonist via activated intracellular reactive oxygen species.

Tetrandrine is a potent cell autophagy agonist via activated intracellular reactive oxygen species.
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粉防己碱是一种通过激活细胞内活性氧而有效的细胞自噬激动剂。

DOI:
10.1186/2045-3701-5-4
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发表时间:
2015
期刊:
影响因子:
7.5
通讯作者:
Li W
Li W
中科院分区:
生物学2区
文献类型:
--
作者:
Wang H;Liu T;Li L;Wang Q;Yu C;Liu X;Li W

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自噬是一种进化上保守的细胞过程,涉及蛋白质和细胞器的溶酶体降解以及细胞组分的再循环,以确保细胞在外部或内部应激下的存活。大量数据表明,自噬可以成功地靶向治疗多种癌症。我们以前已经证明,粉防己碱,从广泛使用的中药千金藤中分离的双苄基异喹啉生物碱,表现出强大的抗肿瘤作用时,无论是单独使用或与其他药物组合。在本研究中,我们发现粉防己碱是一种广谱有效的自噬激动剂。虽然低剂量粉防己碱治疗不影响细胞活力,但它可以有效地诱导各种细胞系中的自噬,包括癌细胞和非致瘤细胞。自噬抑制剂3-甲基腺嘌呤(3-MA)和氯喹(CQ)可有效阻断汉防己甲素诱导的自噬。此外,粉防己碱显着触发诱导线粒体自噬。其机制与汉防己甲素诱导的细胞内活性氧(ROS)的产生有关,ROS在汉防己甲素诱导的自噬中起关键作用。粉防己碱是一种有效的细胞自噬激动剂,在抗肿瘤治疗和基础科研研究领域有着广泛的应用前景。
Autophagy is an evolutionarily conserved cellular process that involves the lysosomal degradation of proteins and organelles and the recycling of cellular components to ensure cellular survival under external or internal stress. Numerous data has indicated that autophagy can be successfully targeted for the treatment of multiple cancers. We have previously demonstrated that tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the broadly used Chinese medicinal herb Stephaniae tetrandrae, exhibits potent antitumor effects when used either alone or in combination with other drugs. In the present study, we showed that tetrandrine is a broad-spectrum potent autophagy agonist. Although low-dose tetrandrine treatment does not affect cell viability, it can potently induce autophagy in a variety of cell lines, including cancerous cells and nontumorigenic cells. The autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ), effectively blocked tetrandrine-induced autophagy. Moreover, tetrandrine significantly triggered the induction of mitophagy. The underlying mechanisms are associated with the tetrandrine-induced production of intracellular reactive oxygen species (ROS), which plays a critical role in tetrandrine-induced autophagy. Here, we report that tetrandrine is a potent cell autophagy agonist and may have a wide range of applications in the fields of antitumor therapy and basic scientific research.
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发表时间: 2013-01-19
期刊: REDOX BIOLOGY
影响因子: 11.4
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