华中师范大学学报(自然科学版)2024,Vol.58Issue(2) :206-213.DOI:10.19603/j.cnki.1000-1190.2024.02.007

华泽兰内生真菌Aspergillus puniceus次级代谢产物及其抗三阴性乳腺癌活性和作用机制

Secondary metabolites of endophytic fungus Aspergillus puniceus from Eupatorium chinense and its anti-triple negative breast cancer activity and mechanism

魏敏 陈莲 陈剑锋 金桂兰 徐帮 王倩 邹坤 程凡 刘呈雄
华中师范大学学报(自然科学版)2024,Vol.58Issue(2) :206-213.DOI:10.19603/j.cnki.1000-1190.2024.02.007

华泽兰内生真菌Aspergillus puniceus次级代谢产物及其抗三阴性乳腺癌活性和作用机制

Secondary metabolites of endophytic fungus Aspergillus puniceus from Eupatorium chinense and its anti-triple negative breast cancer activity and mechanism

魏敏 1陈莲 1陈剑锋 1金桂兰 2徐帮 2王倩 3邹坤 1程凡 1刘呈雄1
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作者信息

  • 1. 三峡大学生物与制药学院,天然产物研究与利用湖北省重点实验室,湖北宜昌 443002
  • 2. 宜昌市第一人民医院,三峡大学附属人民医院,湖北宜昌 443002
  • 3. 宜昌人福药业有限责任公司,湖北宜昌 443002
  • 折叠

摘要

从华泽兰根部分离得到一株内生真菌Aspergillus puniceus.采用正相硅胶柱色谱、Sephadex LH-20凝胶柱色谱及半制备高效液相色谱等方法,从该菌株的发酵液中分离得到8个结构类似的口山酮类化合物,通过现代波谱技术分别鉴定为3',4'-hydrogenated austocystins A(1)、austocystin M(2)、austocystin F(3)、austocystin D(4)、austocystin B(5)、austocystin K(6)、austocystin A(7)、austocystin H(8).MTT结果显示化合物5对三阴性乳腺癌MDA-MB-231细胞具有较好的选择性细胞毒活性(IC50为1.28 μmol·L-1).另外,流式细胞术检测化合物5作用于MDA-MB-231细胞后凋亡率的变化,相比于对照组,最高总凋亡率为69.7%.同时,AO/EB双荧光染色也证明化合物5能够诱导MDA-MB-231的细胞凋亡.JC-1线粒体膜电位检测进一步显示化合物5能够通过线粒体途径诱导三阴性乳腺癌MDA-MB-231的细胞凋亡.

Abstract

An endophytic fungus Aspergillus puniceus was isolated from the root fermentation of Eupatorium chinense.Eight structurally similar xanthones were isolated from the fermentation broth of the strain by normal phase silica gel column chromatography,Sephadex LH-20 gel column chromatography and semi-preparative high performance liquid chromatography.3',4'-hydrogenated austocystins A(1),austocystin M(2),austocystin F(3),austocystin D(4),austocystin B(5),austocystin K(6),austocystin A(7),austocystin H(8)were identified by modern spectroscopic techniques.MTT assay showed that compound 5 had a preferably selective cytotoxicity against triple-negative breast cancer MDA-MB-231 cells with IC50 of 1.28 μmol·L-1.In addition,flow cytometry was used to detect the change of apoptosis rate of MDA-MB-231 cells after treated with compound 5.Compared with the control group,the highest total apoptosis rate was 69.7%.Meanwhile,AO/EB double fluorescence staining also confirmed that compound 5 could induce apoptosis of MDA-MB-231 cells.Mitochondrial membrane potential detection of JC-1 further showed that compound 5 induced apoptosis in MDA-MB-231 cells through mitochondrial pathway.

关键词

华泽兰/Aspergillus/puniceus/次级代谢产物/口山酮/三阴性乳腺癌/凋亡

Key words

Eupatorium chinense/Aspergillus puniceus/secondary metabolites/xanthone/TNBC/apoptosis

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基金项目

湖北省中医药管理局中医药科研项目(ZY2023F083)

天然产物研究与利用湖北省重点实验室(三峡大学)开放基金项目(2022NPRD03)

出版年

2024
华中师范大学学报(自然科学版)
华中师范大学

华中师范大学学报(自然科学版)

CSTPCD北大核心
影响因子:0.512
ISSN:1000-1190
参考文献量18
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