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Mar. Drugs 2015, 13(10), 6259-6273; doi:10.3390/md13106259

Gliotoxin Inhibits Proliferation and Induces Apoptosis in Colorectal Cancer Cells

1
Guangdong Institute of Gastroenterology and the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong, China
2
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou 510655, Guangdong, China
3
Institute of Human Virology and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, China
4
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China
5
Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
These authors contributed equally to this work.
Current affiliation: Japan Agency for Medical Research and Development (AMED), Tokyo 100-0004, Japan.
*
Authors to whom correspondence should be addressed.
Academic Editor: Paul Long
Received: 26 June 2015 / Revised: 27 August 2015 / Accepted: 24 September 2015 / Published: 2 October 2015
(This article belongs to the Special Issue Marine Secondary Metabolites)
View Full-Text   |   Download PDF [1668 KB, uploaded 2 October 2015]   |  

Abstract

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. View Full-Text
Keywords: gliotoxin; marine secondary metabolites; anti-tumor activity; Wnt signaling pathway; colorectal cancer; proliferation; apoptosis gliotoxin; marine secondary metabolites; anti-tumor activity; Wnt signaling pathway; colorectal cancer; proliferation; apoptosis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Chen, J.; Wang, C.; Lan, W.; Huang, C.; Lin, M.; Wang, Z.; Liang, W.; Iwamoto, A.; Yang, X.; Liu, H. Gliotoxin Inhibits Proliferation and Induces Apoptosis in Colorectal Cancer Cells. Mar. Drugs 2015, 13, 6259-6273.

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