Open Access

Avicularin ameliorates human hepatocellular carcinoma via the regulation of NF‑κB/COX‑2/PPAR‑γ activities

  • Authors:
    • Zhimin Wang
    • Fang Li
    • Yuan Quan
    • Junye Shen
  • View Affiliations

  • Published online on: April 25, 2019     https://doi.org/10.3892/mmr.2019.10198
  • Pages: 5417-5423
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) has become a global public health problem. Therefore, the development of novel and effective therapeutic agents for the treatment of HCC is considered an emergency. Avicularin, a bio‑active flavonoid from plants, has been reported to exhibit diverse pharmacological properties. The aim of the present study was to investigate the role of avicularin in HCC and the underlying mechanism of action. Huh7 cells were treated with avicularin in a concentration‑dependent manner, and the cell proliferation was examined using a 3‑(4, 5‑dimethylthiazol‑2‑yl)‑2, 5‑diphenyltetrazolium bromide assay kit. The cell migration and invasion abilities were detected using wounding‑healing assays and Transwell assays. Flow cytometric analysis was performed to investigate the cell cycle distribution and cell apoptosis. The activity of nuclear factor (NF)‑κB (p65), cyclooxygenase‑2 (COX‑2) and peroxisome proliferator‑activated receptor γ (PPAR‑γ) were measured by reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. The results indicated that avicularin treatment markedly decreased cell proliferation concentration‑dependently in HCC, and inhibited cell migration and invasion in Huh7 cells. It was also found that the treatment of avicularin markedly inhibited the G0/G1‑phase cells and decreased the accumulation of S‑phase cells in the cell cycle and induced cell apoptosis. In addition, it was confirmed that the anticancer efficacy of avicularin in HCC was dependent on the regulation of NF‑κB (p65), COX‑2 and PPAR‑γ activities. In conclusion, the findings suggested that avicularin serves an antineoplastic role in HCC and may provide a potential therapeutic strategy for the treatment of HCC.

References

1 

Lu T, Seto WK, Zhu RX, Lai CL and Yuen MF: Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection. World J Gastroenterol. 19:8887–8894. 2003. View Article : Google Scholar

2 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

3 

El-Serag HB and Rudolph KL: Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Yang JD and Roberts LR: Hepatocellular carcinoma: A global view. Nat Rev Gastroenterol Hepatol. 7:448–458. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Jiang X, Feng K, Zhang Y, Li Z, Zhou F, Dou H and Wang T: Sorafenib and DE605, a novel c-Met inhibitor, synergistically suppress hepatocellular carcinoma. Oncotarget. 6:12340–12356. 2015.PubMed/NCBI

6 

Cui X, Wang Y, Kokudo N, Fang D and Tang W: Traditional Chinese medicine and related active compounds against hepatitis B virus infection. Biosci Trends. 4:39–47. 2010.PubMed/NCBI

7 

Williams RJ, Spencer JP and Rice-Evans C: Flavonoids: Antioxidants or signalling molecules? Free Radic Biol Med. 36:838–849. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Handoussa H, Osmanova N, Ayoub N and Mahran L: Spicatic acid: A 4-carboxygentisic acid from Gentiana spicata extract with potential hepatoprotective activity. Drug Discov Ther. 3:278–286. 2009.PubMed/NCBI

9 

Fujimori K and Shibano M: Avicularin, a plant flavonoid, suppresses lipid accumulation through repression of C/EBPα-activated GLUT4-mediated glucose uptake in 3T3-L1 cells. J Agric Food Chem. 61:5139–5147. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Vo VA, Lee JW, Chang JE, Kim JY, Kim NH, Lee HJ, Kim SS, Chun W and Kwon YS: Avicularin inhibits lipopolysaccharide-induced inflammatory response by suppressing ERK phosphorylation in RAW 264.7 macrophages. Biomol Ther (Seoul). 20:532–537. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Guo XF, Liu JP, Ma SQ, Zhang P and Sun WD: Avicularin reversed multidrug-resistance in human gastric cancer through enhancing Bax and BOK expressions. Biomed Pharmacother. 103:67–74. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Srivastava S, Somasagara RR, Hegde M, Nishana M, Tadi SK, Srivastava M, Choudhary B and Raghavan SC: Quercetin, a natural flavonoid interacts with DNA, Arrests cell cycle and causes tumor regression by activating mitochondrial pathway of apoptosis. Sci Rep. 6:240492016. View Article : Google Scholar : PubMed/NCBI

13 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Lang L: FDA approves sorafenib for patients with inoperable liver cancer. Gastroenterology. 134:3792008. View Article : Google Scholar

15 

Hahn O and Stadler W: Sorafenib. Curr Opin Oncol. 18:615–621. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Echeverria V, Burgess S, Gamble-George J, Zeitlin R, Lin X, Cao C and Arendash GW: Sorafenib inhibits nuclear factor kappa B, decreases inducible nitric oxide synthase and cyclooxygenase-2 expression, and restores working memory in APPswe mice. Neuroscience. 162:1220–1231. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K and van Leeuwen PA: Flavonoids: A review of probable mechanisms of action and potential applications. Am J Clin Nutr. 74:418–425. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Chen CH, Huang TS, Wong CH, Hong CL, Tsai YH, Liang CC, Lu FJ and Chang WH: Synergistic anti-cancer effect of baicalein and silymarin on human hepatoma HepG2 cells. Food Chem Toxicol. 47:638–644. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Liu B and Yu S: Amentoflavone suppresses hepatocellular carcinoma by repressing hexokinase 2 expression through inhibiting JAK2/STAT3 signaling. Biomed Pharmacother. 107:243–253. 2018. View Article : Google Scholar : PubMed/NCBI

20 

Liang RR, Zhang S, Qi JA, Wang ZD, Li J, Liu PJ, Huang C, Le XF, Yang J and Li ZF: Preferential inhibition of hepatocellular carcinoma by the flavonoid Baicalein through blocking MEK-ERK signaling. Int J Oncol. 41:969–978. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Jiang CP, Ding H, Shi DH, Wang YR, Li EG and Wu JH: Pro-apoptotic effects of tectorigenin on human hepatocellular carcinoma HepG2 cells. World J Gastroenterol. 18:1753–1764. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Garcia ER, Gutierrez EA, de Melo FCSA, Novaes RD and Goncalves RV: Flavonoids effects on hepatocellular carcinoma in murine models: A systematic review. Evid Based Complement Alternat Med. 2018:63289702018. View Article : Google Scholar : PubMed/NCBI

23 

Gilmore TD: Introduction to NF-kappaB: Players, pathways, perspectives. Oncogene. 25:6680–6684. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Kim JH, Na HK, Pak YK, Lee YS, Lee SJ, Moon A and Surh YJ: Roles of ERK and p38 mitogen-activated protein kinases in phorbol ester-induced NF-kappaB activation and COX-2 expression in human breast epithelial cells. Chem Biol Interact. 171:133–141. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Koeffler HP: Peroxisome proliferator-activated receptor gamma and cancers. Clin Cancer Res. 9:1–9. 2003.PubMed/NCBI

26 

Vara D, Morell C, Rodriguez-Henche N and Diaz-Laviada I: Involvement of PPARgamma in the antitumoral action of cannabinoids on hepatocellular carcinoma. Cell Death Dis. 4:e6182013. View Article : Google Scholar : PubMed/NCBI

27 

Li S, Li J, Fei BY, Shao D, Pan Y, Mo ZH, Sun BZ, Zhang D, Zheng X, Zhang M, et al: MiR-27a promotes hepatocellular carcinoma cell proliferation through suppression of its target gene peroxisome proliferator-activated receptor γ. Chin Med J (Engl). 128:941–947. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Galli A, Ceni E, Mello T, Polvani S, Tarocchi M, Buccoliero F, Lisi F, Cioni L, Ottanelli B, Foresta V, et al: Thiazolidinediones inhibit hepatocarcinogenesis in hepatitis B virus-transgenic mice by peroxisome proliferator-activated receptor gamma-independent regulation of nucleophosmin. Hepatology. 52:493–505. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Yu J, Shen B, Chu ES, Teoh N, Cheung KF, Wu CW, Wang S, Lam CN, Feng H, Zhao J, et al: Inhibitory role of peroxisome proliferator-activated receptor gamma in hepatocarcinogenesis in mice and in vitro. Hepatology. 51:2008–2019. 2010. View Article : Google Scholar : PubMed/NCBI

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June 2019
Volume 19 Issue 6

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Copy and paste a formatted citation
APA
Wang, Z., Li, F., Quan, Y., & Shen, J. (2019). Avicularin ameliorates human hepatocellular carcinoma via the regulation of NF‑κB/COX‑2/PPAR‑γ activities. Molecular Medicine Reports, 19, 5417-5423. https://doi.org/10.3892/mmr.2019.10198
MLA
Wang, Z., Li, F., Quan, Y., Shen, J."Avicularin ameliorates human hepatocellular carcinoma via the regulation of NF‑κB/COX‑2/PPAR‑γ activities". Molecular Medicine Reports 19.6 (2019): 5417-5423.
Chicago
Wang, Z., Li, F., Quan, Y., Shen, J."Avicularin ameliorates human hepatocellular carcinoma via the regulation of NF‑κB/COX‑2/PPAR‑γ activities". Molecular Medicine Reports 19, no. 6 (2019): 5417-5423. https://doi.org/10.3892/mmr.2019.10198