Inhibitory effect of emodin on fatty acid synthase, colon cancer proliferation and apoptosis

Lee,Kyung Ha; Lee,Myung Sun; Cha,Eun Young; Sul,Ji Young; Lee,Jin Sun; Kim,Jin Su; Park,Jun Beom; Kim,Ji Yeon

doi:10.3892/mmr.2017.6254

Inhibitory effect of emodin on fatty acid synthase, colon cancer proliferation and apoptosis

Authors:
- Kyung Ha Lee
- Myung Sun Lee
- Eun Young Cha
- Ji Young Sul
- Jin Sun Lee
- Jin Su Kim
- Jun Beom Park
- Ji Yeon Kim
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Affiliations: Department of Surgery, Chungnam National University Hospital, Daejeon 301‑721, Republic of Korea, Surgical Oncology Research Laboratory, Biomedical Research Institute, Chungnam National University Hospital, Daejeon 301‑721, Republic of Korea
Published online on: February 28, 2017 https://doi.org/10.3892/mmr.2017.6254
Pages: 2163-2173
Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fatty acid synthase (FASN) is a key anabolic enzyme for de novo fatty acid synthesis, which is important in the development of colon carcinoma. The high expression of FASN is considered a promising molecular target for colon cancer therapy. Emodin, a naturally occurring anthraquinone, exhibits an anticancer effect in various types of human cancer, including colon cancer; however, the molecular mechanisms remain to be fully elucidated. Cell viability was evaluated using a Cell Counting Kit‑8 assay. The apoptosis rate of cells was quantified via flow cytometry following Annexin V/propidium iodide staining. FASN activity was measured by monitoring oxidation of nicotinamide adenine dinucleotide phosphate at a wavelength of 340 nm, and intracellular free fatty acid levels were detected using a Free Fatty Acid Quantification kit. Western blot analysis and reverse transcription‑polymerase chain reaction were used to detect target gene and protein expression. The present study was performed to investigate whether the gene expression of FASN and its enzymatic activity are regulated by emodin in a human colon cancer cell line. Emodin markedly inhibited the proliferation of HCT116 cells and a higher protein level of FASN was expressed, compared with that in SW480, SNU-C2A or SNU‑C5 cells. Emodin significantly downregulated the protein expression of FASN in HCT116 cells, which was caused by protein degradation due to elevated protein ubiquitination. Emodin also inhibited intracellular FASN enzymatic activity and reduced the levels of intracellular free fatty acids. Emodin enhanced antiproliferation and apoptosis in a dose‑ and time‑dependent manner. The combined treatment of emodin and cerulenin, a commercial FASN inhibitor, had an additive effect on these activities. Palmitate, the final product of the FASN reaction, rescued emodin‑induced viability and apoptosis. In addition, emodin altered FASN‑involved signaling pathways, including phosphatidylinositol 3-kinase/Akt and mitogen‑activated protein kinases/extracellular signal-regulated kinases 1/2. These results suggested that emodin-regulated cell growth and apoptosis were mediated by inhibiting FASN and provide a molecular basis for colon cancer therapy.

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