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Journal of Gastroenterology

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01.02.2013 | Original Article—Alimentary Tract

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

verfasst von: Hiu-Yee Kwan, Zhijun Yang, Wang-Fun Fong, Yong-Mei Hu, Zhi-Ling Yu, Wen-Luan Wendy Hsiao

Erschienen in: Journal of Gastroenterology | Ausgabe 2/2013

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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.

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Titel: The anticancer effect of oridonin is mediated by fatty acid synthase suppression in human colorectal cancer cells
verfasst von: Hiu-Yee Kwan
Zhijun Yang
Wang-Fun Fong
Yong-Mei Hu
Zhi-Ling Yu
Wen-Luan Wendy Hsiao
Publikationsdatum: 01.02.2013
Verlag: Springer Japan
Erschienen in: Journal of Gastroenterology / Ausgabe 2/2013
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-012-0612-1

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