Fumigaclavine C from a marine-derived fungus Aspergillus fumigatus induces apoptosis in MCF-7 breast cancer cells.
Fumigaclavine C from a marine-derived fungus Aspergillus fumigatus induces apoptosis in MCF-7 breast cancer cells.
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来自海洋源性真菌烟曲霉的 Fumigaclavine C 诱导 MCF-7 乳腺癌细胞凋亡
DOI：
10.3390/md11125063
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发表时间：
2013-12-13
期刊：
影响因子：
5.4
通讯作者：
Kim SK
中科院分区：
文献类型：
--
作者：
Li YX;Himaya SW;Dewapriya P;Zhang C;Kim SK
最近，人们对发现天然化合物作为有效的抗癌候选物给予了极大的关注。在本研究中，从海洋源性真菌烟曲霉中分离出的烟曲霉素 C 的抗癌作用在体外进行了评估。为了探讨烟加棒碱C对乳腺癌细胞增殖抑制和诱导凋亡的影响，用不同浓度的烟加棒碱C处理MCF-7细胞，发现烟加棒碱C对MCF-7细胞表现出明显的细胞毒性。通过细胞流动性和丝裂原激活蛋白激酶（MAPK）信号通路分析抗增殖作用。此外，fumigaclavine C 对 MCF-7 细胞中 MMP-2、-9 的蛋白和基因水平表达具有有效抑制作用，这一点在 Western blot 和逆转录聚合酶链反应 (RT-PCR) 结果中得到体现。通过凋亡相关蛋白表达分析、细胞周期分析、DNA片段化和分子对接研究，研究了fumigaclvine C的凋亡诱导能力。研究发现，fumigaclavine C 使 MCF-7 细胞 DNA 片段化，并通过调节凋亡蛋白表达来阻止细胞周期。此外，fumigaclavine C 显着下调 NF-kappa-B 细胞存活途径。总的来说，数据表明烟加棒碱 C 有潜力被开发为乳腺癌的治疗候选药物。
Recently, much attention has been given to discovering natural compounds as potent anti-cancer candidates. In the present study, the anti-cancer effects of fumigaclavine C, isolated from a marine-derived fungus, Aspergillus fumigatus, was evaluated in vitro. In order to investigate the impact of fumigaclavine C on inhibition of proliferation and induction of apoptosis in breast cancer, MCF-7 cells were treated with various concentrations of fumigaclavine C, and fumigaclavine C showed significant cytotoxicity towards MCF-7 cells. Anti-proliferation was analyzed via cell mobility and mitogen-activated protein kinase (MAPK) signaling pathway. In addition, fumigaclavine C showed potent inhibition on the protein and gene level expressions of MMP-2, -9 in MCF-7 cells which were manifested in Western blot and reverse transcription polymerase chain reaction (RT-PCR) results. The apoptosis induction abilities of the fumigaclvine C was studied by analyzing the expression of apoptosis related proteins, cell cycle analysis, DNA fragmentation and molecular docking studies. It was found that fumigaclavine C fragmented the MCF-7 cell DNA and arrested the cell cycle by modulating the apoptotic protein expressions. Moreover, fumigaclavine C significantly down-regulated the NF-kappa-B cell survival pathway. Collectively, data suggest that fumigaclavine C has a potential to be developed as a therapeutic candidate for breast cancer.
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