Gliotoxin Inhibits Proliferation and Induces Apoptosis in Colorectal Cancer Cells

Marine Drugs

Junxiong Chen¹  Chenliang Wang¹  Wenjian Lan²  Chunying Huang¹  Mengmeng Lin¹  Zhongyang Wang¹  Wanling Liang²  Aikichi Iwamoto³  Xiangling Yang¹  Huanliang Liu¹ 

[1] Guangdong Institute of Gastroenterology and the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong, China; E-Mails:;School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China; E-Mails:;Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; E-Mail:

关键词: gliotoxin;    marine secondary metabolites;    anti-tumor activity;    Wnt signaling pathway;    colorectal cancer;    proliferation;    apoptosis;   

DOI  :  10.3390/md13106259

来源: mdpi

【 摘 要 】

The discovery of new bioactive compounds from marine natural sources is very important in pharmacological research. Here we developed a Wnt responsive luciferase reporter assay to screen small molecule inhibitors of cancer associated constitutive Wnt signaling pathway. We identified that gliotoxin (GTX) and some of its analogues, the secondary metabolites from marine fungus Neosartorya pseufofischeri, acted as inhibitors of the Wnt signaling pathway. In addition, we found that GTX downregulated the β-catenin levels in colorectal cancer cells with inactivating mutations of adenomatous polyposis coli (APC) or activating mutations of β-catenin. Furthermore, we demonstrated that GTX induced growth inhibition and apoptosis in multiple colorectal cancer cell lines with mutations of the Wnt signaling pathway. Together, we illustrated a practical approach to identify small-molecule inhibitors of the Wnt signaling pathway and our study indicated that GTX has therapeutic potential for the prevention or treatment of Wnt dependent cancers and other Wnt related diseases.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.