Hirsutanol A, a novel sesquiterpene compound from fungus Chondrostereum sp., induces apoptosis and inhibits tumor growth through mitochondrial-independent ROS production: hirsutanol A inhibits tumor growth through ROS production.
Hirsutanol A, a novel sesquiterpene compound from fungus Chondrostereum sp., induces apoptosis and inhibits tumor growth through mitochondrial-independent ROS production: hirsutanol A inhibits tumor growth through ROS production.
复制标题
Hirsutanol A 是一种来自真菌 Chondrostereum sp. 的新型倍半萜化合物，通过不依赖线粒体的 ROS 产生诱导细胞凋亡并抑制肿瘤生长：Hirsutanol A 通过 ROS 产生抑制肿瘤生长
DOI：
10.1186/1479-5876-11-32
复制
发表时间：
2013-02-08
影响因子：
7.4
通讯作者：
Zhu XF
中科院分区：
文献类型：
--
作者：
Yang F;Chen WD;Deng R;Zhang H;Tang J;Wu KW;Li DD;Feng GK;Lan WJ;Li HJ;Zhu XF
背景
Hirsutanol A 是一种从真菌 Chondrostereum sp. 中纯化的新型倍半萜化合物。存在于 Tortuosum 石藻中。我们之前的研究表明，hirsutanol A 对多种癌细胞系表现出有效的细胞毒作用。本研究对hirsutanol A的抗肿瘤活性及其分子机制进行了研究。
方法
分别采用MTT法和流式细胞术测定Hirsutanol A诱导的人结肠癌SW620细胞和人乳腺癌MDA-MB-231细胞的生长抑制和细胞凋亡。还通过流式细胞术测定了hirsuanol A对不同细胞系内在ROS水平和线粒体膜电位（△ψm）变化的影响。 JNK siRNA 或 JNK 抑制剂 SP600125 损害了 JNK 的功能。 Western blot分析检测hirsutanol A处理后细胞色素c、p-JNK、p-c-Jun的表达。最后，在人癌细胞SW620异种移植模型中检测了hirsutanol A的体内抗肿瘤作用。
结果
结果表明，hirsuanol A 显着诱导人类癌细胞凋亡、线粒体独立的活性氧 (ROS) 水平增加、线粒体膜电位变化、细胞色素 c 释放。使用强效抗氧化剂 N-乙酰基-L-半胱氨酸 (NAC) 防止 ROS 水平增加，可显着减少 hirsutanol A 诱导的细胞凋亡。此外，hirsutanol A 通过提高 ROS 水平来激活 JNK 信号通路。 JNK 特异性抑制剂 SP600125 阻断 JNK 信号通路可增强细胞凋亡和 hirsutanol A 诱导的 ROS 积累。此外，hirsutanol A 在人癌细胞 SW620 异种移植模型中表现出抗肿瘤活性。
结论
这些数据表明，hirsutanol A 通过触发 ROS 产生和细胞凋亡来抑制肿瘤生长。
Background
Hirsutanol A is a novel sesquiterpene compound purified from fungus Chondrostereum sp. in Sarcophyton tortuosum. Our previous studies had demonstrated that hirsutanol A exhibited potent cytotoxic effect on many kinds of cancer cell lines. In the current study, the antitumor activity of hirsutanol A and its molecular mechanisms were investigated.
Methods
Hirsutanol A induced growth inhibition and apoptotic cell death of human colon cancer SW620 cells and human breast cancer MDA-MB-231cells were determined using MTT assay and flow cytometry assay, respectively. The effect of hirsutanol A on intrinsic ROS level and change in mitochondrial membrane potential (△ψm) of different cell lines were also measured by flow cytometry assay. The function of JNK was compromised by JNK siRNA or JNK inhibitor SP600125. The expression of cytochrome c, p-JNK, p-c-Jun after treatment with hirsutanol A were detected by Western blot analysis. Finally, the in vivo anti-tumor effect of hirsutanol A was examined in human cancer cell SW620 xenograft model.
Results
The results showed that hirsutanol A significantly induced apoptosis, mitochondrial-independent increase of Reactive Oxygen Species (ROS) level, change of mitochondrial membrane potential, release of cytochrome c in human cancer cells. Preventing increase of ROS level using the potent antioxidant N-acetyl-L-cysteine (NAC) markedly decreased hirsutanol A-induced apoptosis. In addition, JNK signaling pathway was activated by hirsutanol A through elevating ROS level. Blockade of JNK signaling pathway by JNK specific inhibitor SP600125 enhanced apoptosis and hirsutanol A-induced ROS accumulation. Also, hirsutanol A exhibited antitumor activity in human cancer cell SW620 xenograft model.
Conclusion
These data suggested that hirsutanol A inhibited tumor growth through triggering ROS production and apoptosis.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
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