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

Hiu Yee KWAN, Zhijun YANG, David W F FONG, Yong Mei Hu, Zhiling YU*, Wendy W L HSIAO

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)182-192
Number of pages11
JournalJournal of Gastroenterology
Volume48
Issue number2
DOIs
Publication statusPublished - Feb 2013

Scopus Subject Areas

  • Gastroenterology

User-Defined Keywords

  • Apoptosis
  • Colorectal cancer
  • Fatty acid synthase
  • Oridonin

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