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穿心莲二萜类化合物对BALB/3T3细胞辐射诱导转化具有防护作用。

Andrographis paniculata Diterpenoids Protect against Radiation-Induced Transformation in BALB/3T3 Cells.

作者信息

Nantajit Danupon, Jetawattana Suwimol, Suriyo Tawit, Grdina David J, Satayavivad Jutamaad

机构信息

a   Department of Radiation Oncology, Chulabhorn Hospital, Bangkok, Thailand.

b   Research and International Relations Division, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand.

出版信息

Radiat Res. 2017 Jul;188(1):66-74. doi: 10.1667/RR14698.1. Epub 2017 May 11.

Abstract

One of the most concerning side effects of exposure to radiation are the carcinogenic risks. To reduce the negative effects of radiation, both cytoprotective and radioprotective agents have been developed. However, little is known regarding their potential for suppressing carcinogenesis. Andrographis paniculata , a plant, with multiple medicinal uses that is commonly used in traditional medicine, has three major constituents known to have cellular antioxidant activity: andrographolide (AP1); 14-deoxy-11,12-didehydroandrographolide (AP3); and neoandrographolide (AP4). In our study, we tested these elements for their radioprotective properties as well as their anti-neoplastic effects on transformation using the BALB/3T3 cell model. All three compounds were able to reduce radiation-induced DNA damage. However, AP4 appeared to have superior radioprotective properties compared to the other two compounds, presumably by protecting mitochondrial function. The compound was able to suppress radiation-induced cellular transformation through inhibition of STAT3. Treatment with AP4 also reduced expressions of MMP-2 and MMP-9. These results suggest that AP4 could be further studied and developed into an anti-transformation/carcinogenic drug as well as a radioprotective agent.

摘要

辐射暴露最令人担忧的副作用之一是致癌风险。为了降低辐射的负面影响,人们已经开发出了细胞保护剂和辐射防护剂。然而,对于它们抑制致癌作用的潜力却知之甚少。穿心莲是一种在传统医学中常用的具有多种药用价值的植物,已知有三种主要成分具有细胞抗氧化活性:穿心莲内酯(AP1);14-脱氧-11,12-二脱氢穿心莲内酯(AP3);新穿心莲内酯(AP4)。在我们的研究中,我们使用BALB/3T3细胞模型测试了这些成分的辐射防护特性以及它们对细胞转化的抗肿瘤作用。所有三种化合物都能够减少辐射诱导的DNA损伤。然而,与其他两种化合物相比,AP4似乎具有更强的辐射防护特性,可能是通过保护线粒体功能实现的。该化合物能够通过抑制STAT3来抑制辐射诱导的细胞转化。用AP4处理还降低了MMP-2和MMP-9的表达。这些结果表明,AP4可以进一步研究并开发成一种抗细胞转化/致癌药物以及一种辐射防护剂。

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