Open Access

Curcumin inhibits hepatocellular carcinoma growth by targeting VEGF expression

  • Authors:
    • Zirong Pan
    • Jianmin Zhuang
    • Chenghong Ji
    • Zhezhen Cai
    • Weijia Liao
    • Zhengjie Huang
  • View Affiliations

  • Published online on: February 7, 2018     https://doi.org/10.3892/ol.2018.7988
  • Pages: 4821-4826
  • Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Morbidity and mortality owing to hepatocellular carcinoma (HCC), the most common primary liver cancer, has increased in recent years. Curcumin is a polyphenol compound that has been demonstrated to exert effective antiangiogenic, anti‑inflammatory, antioxidant, and antitumor effects. However, its clinical effects in HCC remain elusive. The main aim of the present study was to determine the antiangiogenic effects of curcumin in HCC. H22HCC cells were treated with different concentrations of curcumin in vitro. In addition, a mouse xenograft model was used and analyzed for expression levels of vascular endothelial growth factor (VEGF) protein and proteins of the phosphoinositide 3‑kinase (PI3K)/AKT serine/threonine kinase 1 (AKT) signaling pathway. Curcumin treatment inhibited H22 cell proliferation and promoted H22 cell apoptosis in a dose‑dependent manner in vitro. In addition, curcumin treatment inhibited tumor growth in vivo at the concentrations of 50 and 100 mg/kg. Furthermore, curcumin treatment significantly decreased VEGF expression and PI3K/AKT signaling. The present findings demonstrated that curcumin inhibited HCC proliferation in vitro and in vivo by reducing VEGF expression.

References

1 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Li M, Zhang W, Wang B, Gao Y, Song Z and Zheng QC: Ligand-based targeted therapy: A novel strategy for hepatocellular carcinoma. Int J Nanomedicine. 11:5645–5669. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Forner A, Reig ME, de Lope CR and Bruix J: Current strategy for staging and treatment: The BCLC update and future prospects. Semin Liver Dis. 30:61–74. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Peters GJ and Honeywell RJ: Drug transport and metabolism of novel anticancer drugs. Expert Opin Drug Metab Toxicol. 11:661–663. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Berretta M, Rinaldi L, Di Benedetto F, Lleshi A, De Re V, Facchini G, De Paoli P and Di Francia R: Angiogenesis inhibitors for the treatment of hepatocellular carcinoma. Front Pharmacol. 7:4282016. View Article : Google Scholar : PubMed/NCBI

6 

Hanahan D and Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 86:353–364. 1996. View Article : Google Scholar : PubMed/NCBI

7 

Di J, Gao K, Qu D, Yang J and Zheng J: Rap2B promotes angiogenesis via PI3K/AKT/VEGF signaling pathway in human renal cell carcinoma. Tumour Biol. 39:10104283177016532017. View Article : Google Scholar : PubMed/NCBI

8 

Jurenka JS: Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: A review of preclinical and clinical research. Altern Med Rev. 14:141–153. 2009.PubMed/NCBI

9 

Jiao D, Wang J, Lu W, Tang X, Chen J, Mou H and Chen QY: Curcumin inhibited HGF-induced EMT and angiogenesis through regulating c-Met dependent PI3K/Akt/mTOR signaling pathways in lung cancer. Mol Ther Oncolytics. 3:160182016. View Article : Google Scholar : PubMed/NCBI

10 

Haryuna TS, Munir D, Maria A and Bashiruddin J: The antioxidant effect of curcumin on cochlear fibroblasts in rat models of diabetes mellitus. Iran J Otorhinolaryngol. 29:197–202. 2017.PubMed/NCBI

11 

Zhang CY, Zhang L, Yu HX, Bao JD and Lu RR: Curcumin inhibits the metastasis of K1 papillary thyroid cancer cells via modulating E-cadherin and matrix metalloproteinase-9 expression. Biotechnol Lett. 35:995–1000. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Lin J, Deng H, Jin L, Pandey P, Quinn J, Cantin S, Rynkiewicz MJ, Gorga JC, Bibbins F, Celatka CA, et al: Design, synthesis, and biological evaluation of peptidomimetic inhibitors of factor XIa as novel anticoagulants. J Med Chem. 49:7781–7791. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Chen WC, Lai YA, Lin YC, Ma JW, Huang LF, Yang NS, Ho CT, Kuo SC and Way TD: Curcumin suppresses doxorubicin-induced epithelial-mesenchymal transition via the inhibition of TGF-β and PI3K/AKT signaling pathways in triple-negative breast cancer cells. J Agric Food Chem. 61:11817–11824. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Abouzied MM, Eltahir HM, Abdel Aziz MA, Ahmed NS, Abd El-Ghany AA, Abd El-Aziz EA and Abd El-Aziz HO: Curcumin ameliorate DENA-induced HCC via modulating TGF-β, AKT, and caspase-3 expression in experimental rat model. Tumour Biol. 36:1763–1771. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Schneider CA, Rasband WS and Eliceiri KW: NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 9:671–675. 2012. View Article : Google Scholar : PubMed/NCBI

16 

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

17 

Whittaker S, Marais R and Zhu AX: The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene. 29:4989–5005. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Mogler C, König C, Wieland M, Runge A, Besemfelder E, Komljenovic D, Longerich T, Schirmacher P and Augustin HG: Hepatic stellate cells limit hepatocellular carcinoma progression through the orphan receptor endosialin. EMBO Mol Med. 9:741–749. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Hu A, Huang JJ, Jin XJ, Li JP, Tang YJ, Huang XF, Cui HJ, Xu WH and Sun GB: Curcumin suppresses invasiveness and vasculogenic mimicry of squamous cell carcinoma of the larynx through the inhibition of JAK-2/STAT-3 signaling pathway. Am J Cancer Res. 5:278–288. 2014.PubMed/NCBI

20 

Zhu AX: Systemic therapy of advanced hepatocellular carcinoma: How hopeful should we be? Oncologist. 11:790–800. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Farhangi B, Alizadeh AM, Khodayari H, Khodayari S, Dehghan MJ, Khori V, Heidarzadeh A, Khaniki M, Sadeghiezadeh M and Najafi F: Protective effects of dendrosomal curcumin on an animal metastatic breast tumor. Eur J Pharmacol. 758:188–196. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Kumar P, Kadakol A, Shasthrula PK, Mundhe NA, Jamdade VS, Barua CC and Gaikwad AB: Curcumin as an adjuvant to breast cancer treatment. Anticancer Agents Med Chem. 15:647–656. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Wang Z, Dabrosin C, Yin X, Fuster MM, Arreola A, Rathmell WK, Generali D, Nagaraju GP, El-Rayes B, Ribatti D, et al: Broad targeting of angiogenesis for cancer prevention and therapy. Semin Cancer Biol. 35 Suppl:S224–S243. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

April 2018
Volume 15 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Pan, Z., Zhuang, J., Ji, C., Cai, Z., Liao, W., & Huang, Z. (2018). Curcumin inhibits hepatocellular carcinoma growth by targeting VEGF expression. Oncology Letters, 15, 4821-4826. https://doi.org/10.3892/ol.2018.7988
MLA
Pan, Z., Zhuang, J., Ji, C., Cai, Z., Liao, W., Huang, Z."Curcumin inhibits hepatocellular carcinoma growth by targeting VEGF expression". Oncology Letters 15.4 (2018): 4821-4826.
Chicago
Pan, Z., Zhuang, J., Ji, C., Cai, Z., Liao, W., Huang, Z."Curcumin inhibits hepatocellular carcinoma growth by targeting VEGF expression". Oncology Letters 15, no. 4 (2018): 4821-4826. https://doi.org/10.3892/ol.2018.7988