Ergosterol purified from medicinal mushroom Amauroderma rude inhibits cancer growth in vitro and in vivo by up-regulating multiple tumor suppressors.
Ergosterol purified from medicinal mushroom Amauroderma rude inhibits cancer growth in vitro and in vivo by up-regulating multiple tumor suppressors.
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DOI：
10.18632/oncotarget.4026
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发表时间：
2015-07-10
期刊：
影响因子：
--
通讯作者：
Yang BB
中科院分区：
文献类型：
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作者：
Li X;Wu Q;Xie Y;Ding Y;Du WW;Sdiri M;Yang BB
我们之前已经在11种不同的细胞系中筛选了13种药用蘑菇的潜在抗癌活性，发现Amauroderma rude的提取物在诱导癌细胞死亡方面发挥了最高的能力。目前的研究旨在纯化介导抗癌细胞活性的分子。对黑皮木粗提物进行分级分离、硅胶色谱和HPLC。我们纯化了一个化合物，并通过EI-MS和NMR鉴定其为麦角甾醇，与其他药用蘑菇相比，该化合物在Amauroderma rude中的表达水平最高。我们发现麦角固醇诱导癌细胞死亡，这是时间和浓度依赖性的。在体内实验中，正常小鼠被注射了小鼠癌细胞系B16，该细胞系具有很强的侵袭性，并严重导致小鼠死亡。我们发现麦角固醇治疗延长了小鼠的存活时间。我们发现，麦角固醇介导的乳腺癌细胞活力的抑制通过凋亡发生，麦角固醇上调肿瘤抑制因子Foxo 3的表达。此外，Foxo 3下游信号分子Fas、FasL、BimL和BimS上调，导致人乳腺癌细胞MDA-MB-231的凋亡。结果提示麦角甾醇是黑皮木中主要的抗癌活性成分，它激活了细胞凋亡信号通路。麦角甾醇可能作为一种潜在的癌症治疗的领导。
We have previously screened thirteen medicinal mushrooms for their potential anti-cancer activities in eleven different cell lines and found that the extract of Amauroderma rude exerted the highest capacity in inducing cancer cell death. The current study aimed to purify molecules mediating the anti-cancer cell activity. The extract of Amauroderma rude was subject to fractionation, silica gel chromatography, and HPLC. We purified a compound and identified it as ergosterol by EI-MS and NMR, which was expressed at the highest level in Amauroderma rude compared with other medicinal mushrooms tested. We found that ergosterol induced cancer cell death, which was time and concentration dependent. In the in vivo experiment, normal mice were injected with murine cancer cell line B16 that is very aggressive and caused mouse death severely. We found that treatment with ergosterol prolonged mouse survival. We found that ergosterol-mediated suppression of breast cancer cell viability occurred through apoptosis and that ergosterol up-regulated expression of the tumor suppressor Foxo3. In addition, the Foxo3 down-stream signaling molecules Fas, FasL, BimL, and BimS were up-regulated leading to apoptosis in human breast cancer cells MDA-MB-231. Our results suggest that ergosterol is the main anti-cancer ingredient in Amauroderma rude, which activated the apoptotic signal pathway. Ergosterol may serve as a potential lead for cancer therapy.