Document Type

Journal Article

Department/Unit

School of Chinese Medicine

Title

The anticancer effect of oridonin is mediated by fatty acid synthase suppression in human colorectal cancer cells

Language

English

Abstract

Background Fatty acid synthase (FAS) inhibitors could be a therapeutic target in cancer treatment. However, only a few FAS inhibitors showing clinical potential have been reported. Oridonin is a diterpenoid isolated from Rabdosia rubescens. Although it has antiproliferative activity in cancers, little was known about its anticancer effect on colorectal cancer. In this regard, we aimed to investigate if oridonin could be a novel FAS inhibitor and its anticancer mechanism in human colorectal cancer cells. Methods Two human colorectal cancer cell lines SW480 and SW620 were used as models for this study. Results We demonstrated that oridonin reduced viability and induced apoptosis in colorectal cancer cells. Knockdown of the expression of FAS in colorectal cancer cells by siRNA induced apoptosis. This led us to examine whether oridonin-induced apoptosis was mediated by FAS suppression in these cells. We found that oridonin effectively inhibited FAS and SREBP1 mRNA and protein expression in human colorectal cancer cells. In a transient reporter assay, oridonin also reduced transcriptional activity of the FAS promoter region containing the SREBP1 binding site. The FAS inhibition was paralleled by reduction in cellular palmitate and stearic acid. Upregulation of SREBP1 and FAS expression by insulin rescued these cells from oridonin- induced apoptosis. Conclusion These results not only provide a novel molecular mechanism for the anticancer effect of oridonin in colorectal cancer, but also suggest oridonin could be a novel FAS inhibitor in cancer treatment. These results strengthen the scientific basis for the therapeutic use of oridonin in colorectal cancer. © Springer 2012.

Keywords

Apoptosis, Colorectal cancer, Fatty acid synthase, Oridonin

Publication Date

2013

Source Publication Title

Journal of Gastroenterology

Volume

48

Issue

2

Start Page

182

End Page

192

Publisher

Springer Verlag

DOI

10.1007/s00535-012-0612-1

Link to Publisher's Edition

http://dx.doi.org/10.1007/s00535-012-0612-1

ISSN (print)

09441174

ISSN (electronic)

14355922

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