Myricetin inhibits migration and invasion of hepatocellular carcinoma MHCC97H cell line by inhibiting the EMT process

Ma,Hongxin; Zhu,Lei; Ren,Jingna; Rao,Benlong; Sha,Maomao; Kuang,Yi; Shen,Weigan; Xu,Zhengxin

doi:10.3892/ol.2019.10998

Myricetin inhibits migration and invasion of hepatocellular carcinoma MHCC97H cell line by inhibiting the EMT process

Authors:
- Hongxin Ma
- Lei Zhu
- Jingna Ren
- Benlong Rao
- Maomao Sha
- Yi Kuang
- Weigan Shen
- Zhengxin Xu
View Affiliations

Affiliations: Department of Pharmacology, Medical School, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
Published online on: October 18, 2019 https://doi.org/10.3892/ol.2019.10998
Pages: 6614-6620
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The recurrence and metastasis of hepatocellular carcinoma (HCC) are a major concern in current research. Epithelial‑mesenchymal transition (EMT) is the leading cause underlying the high mobility and invasiveness of tumor cells. Myricetin is a natural flavonol with various pharmacological activities. The effects of myricetin on the migration and invasion of HCC MHCC97H cells were evaluated in the present study. Wound healing, Transwell migration and invasion assays were used to examine cell migration and invasion. Western blot analysis and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) were used to examine the expression of epithelial (E)‑cadherin, neural (N)‑cadherin and vimentin. The present study aimed to investigate the effects of myricetin on the migration and invasion of HCC MHCC97H cells. It was indicated that myricetin decreased the viability of MHCC97H cells in a concentration and time‑dependent manner, and inhibited MHCC97H cells migration and invasion. As the concentration of myricetin increased, filopodia and lamellipodia in cells weakened and cells were arranged more closely. RT‑qPCR and western blotting revealed that myricetin upregulated E‑cadherin expression and downregulated N‑cadherin. Collectively, the results of the present study demonstrate that myricetin may inhibit the migration and invasion of HCC MHCC97H cells by inhibiting the EMT process.

View Figures

View References

1	Chen JG and Zhang SW: Liver cancer epidemic in China: Past, present and future. Semin Cancer Biol. 21:59–69. 2011. View Article : Google Scholar : PubMed/NCBI
2	Wang H and Chen L: Tumor microenviroment and hepatocellular carcinoma metastasis. J Gastroenterol Hepatol. 28 (Suppl 1):S43–S48. 2013. View Article : Google Scholar
3	Liu T, Zhang S, Chen J, Jiang K, Zhang Q, Guo K and Liu Y: The transcriptional profiling of glycogenes associated with hepatocellular carcinoma metastasis. PLoS One. 9:e1079412014. View Article : Google Scholar : PubMed/NCBI
4	Ricciardi M, Zanotto M, Malpeli G, Bassi G, Perbellini O, Chilosi M, Bifari F and Krampera M: Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells. Br J Cancer. 112:1067–1075. 2015. View Article : Google Scholar : PubMed/NCBI
5	Pawitan Y, Yin L, Setiawan A, Auer G, Smedby KE and Czene K: Distinct effects of anti-inflammatory and anti-thrombotic drugs on cancer characteristics at diagnosis. Eur J Cancer. 51:751–757. 2015. View Article : Google Scholar : PubMed/NCBI
6	Briso EM, Guinea-Viniegra J, Bakiri L, Rogon Z, Petzelbauer P, Eils R, Wolf R, Rincón M, Angel P and Wagner EF: Inflammation-mediated skin tumorigenesis induced by epidermal c-Fos. Genes Dev. 27:1959–1973. 2013. View Article : Google Scholar : PubMed/NCBI
7	Feng J, Chen X, Wang Y, Du Y, Sun Q, Zang W and Zhao G: Myricetin inhibits proliferation and induces apoptosis and cell cycle arrest in gastric cancer cells. Mol Cell Biochem. 408:163–170. 2015. View Article : Google Scholar : PubMed/NCBI
8	Baldo BA and Pham NH: Adverse reactions to targeted and non-targeted chemotherapeutic drugs with emphasis on hypersensitivity responses and the invasive metastatic switch. Cancer Metastasis Rev. 32:723–761. 2013. View Article : Google Scholar : PubMed/NCBI
9	Tong Y, Zhou XM, Wang SJ, Yang Y and Cao YL: Analgesic activity of myricetin isolated from Myrica rubra Sieb. et Zucc. leaves. Arch Pharm Res. 32:527–533. 2009. View Article : Google Scholar : PubMed/NCBI
10	Yuan X, Liu Y, Hua X, Deng X, Sun P, Yu C, Chen L, Yu S, Liu S and Pang H: Myricetin ameliorates the symptoms of collagen-induced arthritis in mice by inhibiting cathepsin K activity. Immunopharmacol Immunotoxicol. 37:513–519. 2015. View Article : Google Scholar : PubMed/NCBI
11	Kandasamy N and Ashokkumar N: Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin-cadmium induced diabetic nephrotoxic rats. Toxicol Appl Pharmacol. 279:173–185. 2014. View Article : Google Scholar : PubMed/NCBI
12	Jose J, Dhanya AT, Haridas KR, Sumesh Kumar TM, Jayaraman S, Variyar EJ and Sudhakaran S: Structural characterization of a novel derivative of myricetin from Mimosa pudica as an anti-proliferative agent for the treatment of cancer. Biomed Pharmacother. 84:1067–1077. 2016. View Article : Google Scholar : PubMed/NCBI
13	Semwal DK, Semwal RB, Combrinck S and Viljoen A: Myricetin: A dietary molecule with diverse biological activities. Nutrients. 8:902016. View Article : Google Scholar : PubMed/NCBI
14	Shih YW, Wu PF, Lee YC, Shi MD and Chiang TA: Myricetin suppresses invasion and migration of human lung adenocarcinoma A549 cells: Possible mediation by blocking the ERK signaling pathway. J Agric Food Chem. 57:3490–3499. 2009. View Article : Google Scholar : PubMed/NCBI
15	Kumamoto T, Fujii M and Hou DX: Myricetin directly targets JAK1 to inhibit cell transformation. Cancer Lett. 275:17–26. 2009. View Article : Google Scholar : PubMed/NCBI
16	Seydi E, Rasekh HR, Salimi A, Mohsenifar Z and Pourahmad J: Myricetin selectively induces apoptosis on cancerous hepatocytes by directly targeting their mitochondria. Basic Clin Pharmacol Toxicol. 119:249–258. 2016. View Article : Google Scholar : PubMed/NCBI
17	Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J and Xue Q: New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer. 81:814–821. 1999. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Meth. 25:402–408. 2001. View Article : Google Scholar
19	Zhao H, Jiao Y and Zhang Z: Deguelin inhibits the migration and invasion of lung cancer A549 and H460 cells via regulating actin cytoskeleton rearrangement. Int J Clin Exp Pathol. 8:15582–15590. 2015.PubMed/NCBI
20	Chen L, Chan TH, Yuan YF, Hu L, Huang J, Ma S, Wang J, Dong SS, Tang KH, Xie D, et al: CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients. J Clin Invest. 120:1178–1191. 2010. View Article : Google Scholar : PubMed/NCBI
21	Lin Z, Li W, Zhang H, Wu W, Peng Y, Zeng Y, Wan Y, Wang J and Ouyang N: CCL18/PITPNM3 enhances migration, invasion, and EMT through the NF-κB signaling pathway in hepatocellular carcinoma. Tumour Biol. 37:3461–3468. 2016. View Article : Google Scholar : PubMed/NCBI
22	Ko CH, Shen SC, Lee TJ and Chen YC: Myricetin inhibits matrix metalloproteinase 2 protein expression and enzyme activity in colorectal carcinoma cells. Mol Cancer Ther. 4:281–290. 2005.PubMed/NCBI
23	De Craene B and Berx G: Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 13:97–110. 2013. View Article : Google Scholar : PubMed/NCBI
24	Jung HY, Fattet L and Yang J: Molecular pathways: Linking tumor microenvironment to epithelial-mesenchymal transition in metastasis. Clin Cancer Res. 21:962–968. 2015. View Article : Google Scholar : PubMed/NCBI