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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

Fen Yang1, Wen-Dan Chen1, Rong Deng1, Hui Zhang3, Jun Tang1, Ke-Wei Wu1, Dan-Dan Li1, Gong-Kan Feng1, Wen-Jian Lan4, Hou-Jin Li2* and Xiao-Feng Zhu1*

Author Affiliations

1 State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, 651 Dongfeng Road East, Guangzhou 510060, China

2 School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China

3 Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

4 School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China

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Journal of Translational Medicine 2013, 11:32  doi:10.1186/1479-5876-11-32

Published: 8 February 2013



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.


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.


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.


These data suggested that hirsutanol A inhibited tumor growth through triggering ROS production and apoptosis.

Hirsutanol A; Apoptosis; JNK; Mitochondria; ROS; Cancer