Tanshinone IIA Inhibits Growth of Keratinocytes through Cell Cycle Arrest and Apoptosis: Underlying Treatment Mechanism of Psoriasis.

Tanshinone IIA Inhibits Growth of Keratinocytes through Cell Cycle Arrest and Apoptosis: Underlying Treatment Mechanism of Psoriasis.
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丹参酮 IIA 通过细胞周期阻滞和细胞凋亡抑制角质形成细胞的生长:银屑病的潜在治疗机制

DOI:
10.1155/2012/927658
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发表时间:
2012
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Li B
Li B
中科院分区:
其他
文献类型:
--
作者:
Li FL;Xu R;Zeng QC;Li X;Chen J;Wang YF;Fan B;Geng L;Li B

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本研究的目的是阐明丹参酮IIA(Tan IIA)在体外导致银屑病靶细胞角质形成细胞周期阻滞和凋亡的细胞机制。Tan IIA以剂量和时间依赖性方式抑制小鼠角质形成细胞的增殖,并诱导凋亡,导致S期阻滞伴随着pCdk 2和cyclin A蛋白表达的下调。此外,谭IIA诱导的细胞凋亡和线粒体膜电位的变化也进一步证明了DNA断裂,单细胞凝胶电泳(SCGE),和流式细胞术的方法。Caspase-3抑制剂Ac-DEVD-CHO可部分阻断细胞凋亡。进一步研究了线粒体对下游细胞凋亡的调节,显示线粒体膜电位的变化、细胞色素c释放到细胞质中以及裂解的半胱天冬酶-3和聚ADP-核糖聚合酶(PARP)的活化增强。在凋亡的角质形成细胞中也没有凋亡诱导因子(AIF)从线粒体易位到细胞核,表明Tan IIA诱导的凋亡主要通过caspase途径发生。我们的研究结果提供了Tan IIA可用于治疗银屑病的分子机制,并支持传统使用丹参(Labiolithium)治疗银屑病和相关皮肤病。
The aim of the present investigation was to elucidate the cellular mechanisms whereby Tanshinone IIA (Tan IIA) leads to cell cycle arrest and apoptosis in vitro in keratinocytes, the target cells in psoriasis. Tan IIA inhibited proliferation of mouse keratinocytes in a dose- and time-dependent manner and induced apoptosis, resulting in S phase arrest accompanied by down-regulation of pCdk2 and cyclin A protein expression. Furthermore, Tan IIA-induced apoptosis and mitochondrial membrane potential changes were also further demonstrated by DNA fragmentation, single-cell gel electrophoresis assay (SCGE), and flow cytometry methods. Apoptosis was partially blocked by the caspase-3 inhibitor Ac-DEVD-CHO. Mitochondrial regulation of apoptosis further downstream was investigated, showing changes in the mitochondrial membrane potential, cytochrome c release into the cytoplasm, and enhanced activation of cleaved caspase-3 and Poly ADP-ribose polymerase (PARP). There was also no translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus in apoptotic keratinocytes, indicating Tan IIA-induced apoptosis occurs mainly through the caspase pathway. Our findings provide the molecular mechanisms by which Tan IIA can be used to treat psoriasis and support the traditional use of Salvia miltiorrhiza Bungee (Labiatae) for psoriasis and related skin diseases.
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