Inhibitory effects of aesculetin on the proliferation of colon cancer cells by the Wnt/β-catenin signaling pathway

Li,Tao; Zhang,Lei; Huo,Xinkai

doi:10.3892/ol.2018.8244

Inhibitory effects of aesculetin on the proliferation of colon cancer cells by the Wnt/β-catenin signaling pathway

Authors:
- Tao Li
- Lei Zhang
- Xinkai Huo
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Affiliations: Department of Oncology, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China, Department of Proctology, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China, Department of Gastrointestinal Surgery, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China
Published online on: March 12, 2018 https://doi.org/10.3892/ol.2018.8244
Pages: 7118-7122
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The inhibitory effect of aesculetin on the growth of colon cancer cell line SW480 through the Wnt/β-catenin signaling pathway was studied. The appropriate concentration of aesculetin was selected by cell counting kit-8 (CCK-8) assay, and the effect of aesculetin on the proliferation of SW480 cells was investigated by bromodeoxyuridine (BrdU) assay. The expression level of the messenger ribonucleic acid (mRNA) in β-catenin and Wnt signaling pathway target genes, c-Myc and cyclin D1, was detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression levels of β-catenin, c-Myc and cyclin D1 proteins were detected by western blotting. CCK-8 detection results showed that compared with the control group, aesculetin effectively inhibited the proliferation of SW480 cells. BrdU detection results indicated that the number of BrdU positive cells in all the groups treated with drugs was significantly decreased. The of RT-PCR results suggested that aesculetin reduced the expression level of β-catenin mRNA and inhibited the expression of mRNA in the Wnt signaling pathway target genes, c-Myc and cyclin D1. Western blotting detection results revealed that aesculetin downregulated the expression level of β-catenin, c-Myc and cyclin D1 proteins. Aesculetin can inhibit tumor growth by suppressing the Wnt signaling pathway. This study provides a new idea and direction for the antitumor mechanism of aesculetin.

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1	Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
3	Olaku O and White JD: Herbal therapy use by cancer patients: A literature review on case reports. Eur J Cancer. 47:508–514. 2011. View Article : Google Scholar : PubMed/NCBI
4	Wang CJ, Hsieh YJ, Chu CY, Lin YL and Tseng TH: Inhibition of cell cycle progression in human leukemia HL-60 cells by esculetin. Cancer Lett. 183:163–168. 2002. View Article : Google Scholar : PubMed/NCBI
5	Chu CY, Tsai YY, Wang CJ, Lin WL and Tseng TH: Induction of a poptosis by esculetin in human leukemia cells. Eur J Pharmacol. 416:25–32. 2001. View Article : Google Scholar : PubMed/NCBI
6	Kuo HC, Lee HJ, Hu CC, Shun HI and Tseng TH: Enhancement of esculetin on Taxol-induced apoptosis in human hepatoma HepG2 cells. Toxicol Appl Pharmacol. 210:55–62. 2006. View Article : Google Scholar : PubMed/NCBI
7	Leung KN, Leung PY, Kong LP and Leung PK: Immunomodulatory effects of esculetin (6,7-dihydroxycoumarin) on murine lymphocytes and peritoneal macrophages. Cell Mol Immunol. 2:181–188. 2005.PubMed/NCBI
8	Kaneko T, Tahara S and Takabayashi F: Inhibitory effect of natural coumarin compounds, esculetin and esculin, on oxidative DNA damage and formation of aberrant crypt foci and tumors induced by 1,2-dimethylhydrazine in rat colons. Biol Pharm Bull. 30:2052–2057. 2007. View Article : Google Scholar : PubMed/NCBI
9	Noguchi M, Earashi M, Minami M, Miyazaki I, Tanaka M and Sasaki T: Effects of piroxicam and esculetin on the MDA-MB-231 human breast cancer cell line. Prostaglandins Leukot Essent Fatty Acids. 53:325–329. 1995. View Article : Google Scholar : PubMed/NCBI
10	Effect of esculetin on proliferation of human heptocellular carcinoma cell line SMMC-7721 in vitro. Chin JMAP. 26:6439–442. 2009.
11	Din FV, Theodoratou E, Farrington SM, Tenesa A, Barnetson RA, Cetnarskyj R, Stark L, Porteous ME, Campbell H and Dunlop MG: Effect of aspirin and NSAIDs on risk and survival from colorectal cancer. Gut. 59:1670–1679. 2010. View Article : Google Scholar : PubMed/NCBI
12	Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL and Massagué J: Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 451:147–152. 2008. View Article : Google Scholar : PubMed/NCBI
13	Miyoshi K and Hennighausen L: Beta-catenin: A transforming actor on many stages. Breast Cancer Res. 5:63–68. 2003. View Article : Google Scholar : PubMed/NCBI
14	Maruyama K, Ochiai A, Akimoto S, Nakamura S, Baba S, Moriya Y and Hirohashi S: Cytoplasmic beta-catenin accumulation as a predictor of hematogenous metastasis in human colorectal cancer. Oncology. 59:302–309. 2000. View Article : Google Scholar : PubMed/NCBI
15	Polakis P: Wnt signaling and cancer. Genes Dev. 14:1837–1851. 2000.PubMed/NCBI
16	Koehler A, Schlupf J, Schneider M, Kraft B, Winter C and Kashef J: Loss of Xenopus cadherin-11 leads to increased Wnt/beta-catenin signaling and up-regulation of target genes c-myc and cyclin D1 in neural crest. Dev Biol. 383:132–145. 2013. View Article : Google Scholar : PubMed/NCBI
17	Lim SC and Lee MS: Significance of E-cadherin/β-catenin complex and cyclin D1 in breast cancer. Oncol Rep. 9:915–928. 2002.PubMed/NCBI
18	Roh MS, Hong SH, Jeong JS, Kwon HC, Kim MC, Cho SH, Yoon JH and Hwang TH: Gene expression profiling of breast cancers with emphasis of beta-catenin regulation. J Korean Med Sci. 19:275–282. 2004. View Article : Google Scholar : PubMed/NCBI
19	Utsuki S, Sato Y, Oka H, Tsuchiya B, Suzuki S and Fujii K: Relationship between the expression of E-, N-cadherins and beta-catenin and tumor grade in astrocytomas. J Neurooncol. 57:187–192. 2002. View Article : Google Scholar : PubMed/NCBI
20	Ehrlich D, Bruder E, Thome MA, Gutt CN, von Knebel Doeberitz M, Niggli F, Perantoni AO and Koesters R: Nuclear accumulation of beta-catenin protein indicates activation of wnt signaling in chemically induced rat nephroblastomas. Pediatr Dev Pathol. 13:1–8. 2010. View Article : Google Scholar : PubMed/NCBI
21	Hu Y, Wang S, Wu X, Zhang J, Chen R, Chen M and Wang Y: Chinese herbal medicine-derived compounds for cancer therapy: A focus on hepatocellular carcinoma. J Ethnopharmacol. 149:601–612. 2013. View Article : Google Scholar : PubMed/NCBI
22	Liu YZ, Wu K, Huang J, Liu Y, Wang X, Meng ZJ, Yuan SX, Wang DX, Luo JY, Zuo GW, et al: The PTEN/PI3K/Akt and Wnt/β-catenin signaling pathways are involved in the inhibitory effect of resveratrol on human colon cancer cell proliferation. Int J Oncol. 45:104–112. 2014. View Article : Google Scholar : PubMed/NCBI