Berberine inhibits Wilms' tumor cell progression through upregulation of Wilms' tumor gene on the X chromosome

Liu,Yan; Liu,Sheng

doi:10.3892/mmr.2013.1665

Berberine inhibits Wilms' tumor cell progression through upregulation of Wilms' tumor gene on the X chromosome

Authors:
- Yan Liu
- Sheng Liu
View Affiliations

Affiliations: Department of Pediatrics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 475000, P.R. China, Department of Pharmacology, Basic Medical College of Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
Published online on: September 3, 2013 https://doi.org/10.3892/mmr.2013.1665
Pages: 1537-1541

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

Wilms' tumor is a type of kidney cancer that affects young children. Although a number of Wilms' tumor samples have been collected through international trials, the mechanisms underlying its progression remain challenging to determine. Extensive studies have identified somatic mutations at several loci in Wilms' tumorigenesis, including WT1, catenin, Wilms' tumor gene on the X chromosome (WTX) and TP53. Berberine is a benzylisoquinoline alkaloid extracted from numerous types of medicinal plants and has been extensively used as a Chinese traditional medicine. Recently, berberine has been demonstrated to possess antitumoral activities. AMP-activated protein kinase (AMPK) is suggested to be one of the various cellular targets of berberine, which regulates tumor progression and metastasis. However, the specific involvement of berberine‑induced AMPK activation and its effects on the proliferation potential of Wilms' tumor cells remains unknown. The present study investigated the berberine‑induced activation of AMPK and its effects on G401 Wilms' tumor cell proliferation. The results demonstrated that berberine inhibited growth and decreased the expression of cell‑cycle regulators in these cells. At the molecular level, berberine treatment led to a significant increase of WTX expression and G401 cells were protected against berberine‑induced growth inhibition by small interfering RNA against WTX. In conclusion, these results suggest a novel mechanism that may contribute to the antineoplastic effects of berberine which was also demonstrated by recent population studies; however, further studies are required to investigate the potential therapeutic use of berberine in patients with Wilms' tumor.

View Figures

View References

1	Scott RH, Stiller CA, Walker L and Rahman N: Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. J Med Genet. 43:705–715. 2006. View Article : Google Scholar : PubMed/NCBI
2	Malkin D, Sexsmith E, Yeger H, Williams BR and Coppes MJ: Mutations of the p53 tumor suppressor gene occur infrequently in Wilms’ tumor. Cancer Res. 54:2077–2079. 1994.PubMed/NCBI
3	Grundy PE, Breslow NE, Li S, et al; National Wilms Tumor Study Group. Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol. 23:7312–7321. 2005. View Article : Google Scholar
4	Rivera MN, Kim WJ, Wells J, et al: An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Science. 315:642–645. 2007. View Article : Google Scholar : PubMed/NCBI
5	Major MB, Camp ND, Berndt JD, et al: Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling. Science. 316:1043–1046. 2007. View Article : Google Scholar : PubMed/NCBI
6	Rivera MN and Haber DA: Wilms’ tumour: connecting tumorigenesis and organ development in the kidney. Nat Rev Cancer. 5:699–712. 2005.
7	Kim WJ, Rivera MN, Coffman EJ and Haber DA: The WTX tumor suppressor enhances p53 acetylation 9 by CBP/p300. Mol Cell. 45:587–597. 2012. View Article : Google Scholar : PubMed/NCBI
8	Hou Q, Tang X, Liu H, et al: Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147. Cancer Sci. 102:1287–1292. 2011. View Article : Google Scholar : PubMed/NCBI
9	James MA, Fu H, Liu Y, Chen DR and You M: Dietary administration of berberine or Phellodendron amurense extract inhibits cell cycle progression and lung tumorigenesis. Mol Carcinog. 50:1–7. 2011.
10	Harikumar KB, Kuttan G and Kuttan R: Inhibition of progression of erythroleukemia induced by Friend virus in BALB/c mice by natural products - berberine, curcumin and picroliv. J Exp Ther Oncol. 7:275–284. 2008.PubMed/NCBI
11	Yan K, Zhang C, Feng J, et al: Induction of G1 cell cycle arrest and apoptosis by berberine in bladder cancer cells. Eur J Pharmacol. 661:1–7. 2011. View Article : Google Scholar : PubMed/NCBI
12	Kim S, Han J, Kim NY, et al: Effect of berberine on p53 expression by TPA in breast cancer cells. Oncol Rep. 27:210–215. 2012.PubMed/NCBI
13	Meeran SM, Katiyar S and Katiyar SK: Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation. Toxicol Appl Pharmacol. 229:33–43. 2008. View Article : Google Scholar : PubMed/NCBI
14	Lv X, Yu X, Wang Y, et al: Berberine inhibits doxorubicin-triggered cardiomyocyte apoptosis via attenuating mitochondrial dysfunction and increasing Bcl-2 expression. PLoS One. 7:e473512012. View Article : Google Scholar
15	Tillhon M, Guamán Ortiz LM, Lombardi P and Scovassi AI: Berberine: new perspectives for old remedies. Biochem Pharmacol. 84:1260–1267. 2012. View Article : Google Scholar : PubMed/NCBI
16	Kim S, Han J, Lee SK, et al: Berberine suppresses the TPA-induced MMP-1 and MMP-9 expressions through the inhibition of PKC-α in breast cancer cells. J Surg Res. 176:e21–e29. 2012.PubMed/NCBI
17	Chitra P, Saiprasad G, Manikandan R and Sudhandiran G: Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-κB dependent TGF-β activation: a biphasic experimental study. Toxicol Lett. 219:178–193. 2013.PubMed/NCBI
18	Alzamora R, O’Mahony F, Ko WH, Yip TW, Carter D, Irnaten M and Harvey BJ: Berberine reduces cAMP-induced chloride secretion in T84 human colonic carcinoma cells through inhibition of basolateral KCNQ1 channels. Front Physiol. 2:332011. View Article : Google Scholar : PubMed/NCBI
19	Kim HS, Kim MJ, Kim EJ, Yang Y, Lee MS and Lim JS: Berberine-induced AMPK activation inhibits the metastatic potential of melanoma cells via reduction of ERK activity and COX-2 protein expression. Biochem Pharmacol. 83:385–394. 2012. View Article : Google Scholar : PubMed/NCBI
20	Kim MK, Min DJ, Rabin M and Licht JD: Functional characterization of Wilms tumor-suppressor WTX and tumor-associated mutants. Oncogene. 30:832–842. 2011. View Article : Google Scholar : PubMed/NCBI
21	Hardie DG: AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev. 25:1895–1908. 2011. View Article : Google Scholar : PubMed/NCBI
22	Egan DF, Shackelford DB, Mihaylova MM, et al: Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 331:456–461. 2011. View Article : Google Scholar : PubMed/NCBI
23	Gwinn DM, Shackelford DB, Egan DF, et al: AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 30:214–226. 2008. View Article : Google Scholar : PubMed/NCBI
24	Liu L, Ulbrich J, Müller J, et al: Deregulated MYC expression induces dependence upon AMPK-related kinase 5. Nature. 483:608–612. 2012. View Article : Google Scholar : PubMed/NCBI
25	Jones RG, Plas DR, Kubek S, et al: AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell. 18:283–293. 2005. View Article : Google Scholar : PubMed/NCBI