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6-甲氧基鬼臼毒素通过抑制5637和K562癌细胞系中TUBB3和TOPIIA基因表达诱导细胞凋亡。

6-Methoxy Podophyllotoxin Induces Apoptosis via Inhibition of TUBB3 and TOPIIA Gene Expressions in 5637 and K562 Cancer Cell Lines.

作者信息

Sadeghi Iman, Behmanesh Mehrdad, Ahmadian Chashmi Najmeh, Sharifi Mohsen, Soltani Bahram Mohammad

机构信息

Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Department of Plant Biology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Cell J. 2015 Fall;17(3):502-9. doi: 10.22074/cellj.2015.10. Epub 2015 Oct 7.

Abstract

OBJECTIVE

Podophyllotoxin (PTOX), a natural compound in numerous plants, contains remarkable biological properties that include anti-tumor, anti-viral such as anti-human im- munodeficiency virus (HIV) activities. In order to avoid its adverse effects, various com- pounds have been derived from PTOX. 6-methoxy PTOX (MPTOX) is one of the natural PTOX derivatives with an extra methoxy group. MPTOX is mostly isolated from the Linum species. This study has sought to determine the biological effects of MPTOX on cancer cell lines, 5637 and K562.

MATERIALS AND METHODS

In this experimental study, we treated the 5637 and K562 cancer cell lines with MPTOX in a doseand time-dependent manner. Apoptosis was examined by flow cytometry and viability rate was analyzed by the MTT assay. Expressions of the tubulin (TUBB3) and topoisomerase II (TOPIIA) genes were determined by real-time poly- merase chain reaction (PCR).

RESULTS

Treatment with MPTOX led to significant induction of apoptosis in cancer cells compared to control cells. Gene expression analysis showed reduced levels of TUBB3 and TOPIIA mRNA following MPTOX treatment.

CONCLUSION

MPTOX inhibited TUBB3 and TOPIIA gene expression and subsequently induced cell death through apoptosis. These results suggested that MPTOX could be considered a potential anti-tumor agent.

摘要

目的

鬼臼毒素(PTOX)是众多植物中的一种天然化合物,具有显著的生物学特性,包括抗肿瘤、抗病毒,如抗人类免疫缺陷病毒(HIV)活性。为避免其不良反应,已从PTOX衍生出多种化合物。6-甲氧基鬼臼毒素(MPTOX)是一种带有额外甲氧基的天然PTOX衍生物。MPTOX大多从亚麻属植物中分离得到。本研究旨在确定MPTOX对癌细胞系5637和K562的生物学作用。

材料与方法

在本实验研究中,我们以剂量和时间依赖性方式用MPTOX处理5637和K562癌细胞系。通过流式细胞术检测细胞凋亡,通过MTT法分析细胞活力率。通过实时聚合酶链反应(PCR)测定微管蛋白(TUBB3)和拓扑异构酶II(TOPIIA)基因的表达。

结果

与对照细胞相比,用MPTOX处理导致癌细胞中凋亡显著诱导。基因表达分析显示,MPTOX处理后TUBB3和TOPIIA mRNA水平降低。

结论

MPTOX抑制TUBB3和TOPIIA基因表达,随后通过凋亡诱导细胞死亡。这些结果表明MPTOX可被视为一种潜在的抗肿瘤药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0b4/4601871/a27b68e4d057/Cell-J-17-502-g01.jpg

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