Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
2014-February Volume 33 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
2014-February Volume 33 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Purified vitexin compound 1 inhibits growth and angiogenesis through activation of FOXO3a by inactivation of Akt in hepatocellular carcinoma

  • Authors:
    • Jiangang Wang
    • Xingxing Zheng
    • Guangyao Zeng
    • Yingjun Zhou
    • Hong Yuan
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, School of Pharmaceutical Science, Central South University, Changsha, Hunan 410013, P.R. China
  • Pages: 441-448
    |
    Published online on: December 12, 2013
       https://doi.org/10.3892/ijmm.2013.1587
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Vitexins, isolated from the seeds of the Chinese herb Vitex negundo, is known to exert antitumor activity in cancer xenograft models and cell lines. The aim of the current study was to examine whether the Akt/forkhead box protein O3a (FOXO3a) pathway mediates the biological effects of purified vitexin compound 1 (VB-1) in hepatocellular carcinoma (HCC) cells. The effect of VB-1 on the viability of the HCC cell lines HepG2, Hep3B, Huh-7 and the human embryonic liver cells L-02 was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Growth inhibition was assessed by clonogenic assay, and cell cycle arrest was investigated using flow cytometry. Inhibition of angiogenesis was evaluated using a matrigel in vitro HUVEC tube formation assay. The effects on the Akt/FOXO3a pathway were detected by western blotting. VB-1 suppressed the proliferation of HepG2, Hep3B, Huh-7 cells, but had little effect on L-02 cells. VB-1 inhibited anchorage-dependent and -independent HepG2 cell growth in a concentration-dependent manner by induction of cell cycle arrest at G1/G0. VB-1 also reduced the secretion of vascular endothelial growth factor (VEGF), resulting in the inhibition of endothelial tube formation. Phosphorylated Akt and its downstream effector FOXO3a were downregulated in VB-1-treated HepG2 cells. Knockdown of Akt1 by small interfering RNA (siRNA) enhanced growth inhibition, and silencing FOXO3a by siRNA attenuated this action. VB-1 inhibited growth and induced cell cycle arrest at G1/G0 by regulating the Akt/FOXO3a pathway. The findings suggested that VB-1 is a potentially promising candidate for the treatment of HCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar

2 

Okuda K: Hepatocellular carcinoma. J Hepatol. 32:225–237. 2000. View Article : Google Scholar

3 

Llovet JM, Burroughs A and Bruix J: Hepatocellular carcinoma. Lancet. 362:1907–1917. 2003. View Article : Google Scholar

4 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Lai EC and Lau WY: The continuing challenge of hepatic cancer in Asia. Surgeon. 3:210–215. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Thompson LU, Chen JM, Li T, Strasser-Weippl K and Goss PE: Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin Cancer Res. 11:3828–3835. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Park JB, Lee MS, Cha EY, et al: Magnolol-induced apoptosis in HCT-116 colon cancer cells is associated with the AMP-activated protein kinase signaling pathway. Biol Pharm Bull. 35:1614–1620. 2012.PubMed/NCBI

8 

Kuijsten A, Arts IC, Hollman PC, van’t Veer P and Kampman E: Plasma enterolignans are associated with lower colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev. 15:1132–1136. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Adlercreutz H: Lignans and human health. Crit Rev Clin Lab Sci. 44:483–525. 2007. View Article : Google Scholar

10 

Bergman Jungestrom M, Thompson LU and Dabrosin C: Flaxseed and its lignans inhibit estradiol-induced growth, angiogenesis, and secretion of vascular endothelial growth factor in human breast cancer xenografts in vivo. Clin Cancer Res. 13:1061–1067. 2007.PubMed/NCBI

11 

Cuca LE, Coy ED, Alarcón MA, Fernández A and Aristizábal FA: Cytotoxic effect of some natural compounds isolated from Lauraceae plants and synthetic derivatives. Biomedica. 31:335–343. 2011.PubMed/NCBI

12 

Zhou Y, Liu YE, Cao J, et al: Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth. Clin Cancer Res. 15:5161–5169. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Liu Z, Xiao Y, Yuan Y, et al: Effects of oleic acid on cell proliferation through an integrin-linked kinase signaling pathway in 786-O renal cell carcinoma cells. Oncol Lett. 5:1395–1399. 2013.PubMed/NCBI

14 

Vene R, Benelli R, Minghelli S, Astigiano S, Tosetti F and Ferrari N: Xanthohumol impairs human prostate cancer cell growth and invasion and diminishes the incidence and progression of advanced tumors in TRAMP mice. Mol Med. 18:1292–1302. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Rubinfeld H, Cohen-Kaplan V, Nass D, et al: Heparanase is highly expressed and regulates proliferation in GH-secreting pituitary tumor cells. Endocrinology. 152:4562–4570. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Wu J, Wu X, Zhong D, Zhai W, Ding Z and Zhou Y: Short hairpin RNA (shRNA) Ether à go-go 1 (Eag1) inhibition of human osteosarcoma angiogenesis via VEGF/PI3K/AKT signaling. Int J Mol Sci. 13:12573–12583. 2012.

17 

Khaidakov M and Mehta JL: Oxidized LDL triggers pro-oncogenic signaling in human breast mammary epithelial cells partly via stimulation of MiR-21. PLoS One. 7:e469732012. View Article : Google Scholar : PubMed/NCBI

18 

van Dijk M, van Bezu J, van Abel D, et al: The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by alpha-T-catenin upregulation. Hum Mol Genet. 19:2658–2667. 2010.PubMed/NCBI

19 

Biggs WH III, Meisenhelder J, Hunter T, Cavenee WK and Arden KC: Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci USA. 96:7421–7426. 1999. View Article : Google Scholar

20 

Band AM, Björklund M and Laiho M: The phosphatidylinositol 3-kinase/Akt pathway regulates transforming growth factor-{beta} signaling by destabilizing ski and inducing Smad7. J Biol Chem. 284:35441–35449. 2009.

21 

Wang L, Jia D, Duan F, et al: Combined anti-tumor effects of IFN-alpha and sorafenib on hepatocellular carcinoma in vitro and in vivo. Biochem Biophys Res Commun. 422:687–692. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Vanbrocklin MW, Robinson JP, Lastwika KJ, McKinney AJ, Gach HM and Holmen SL: Ink4a/Arf loss promotes tumor recurrence following Ras inhibition. Neuro Oncol. 14:34–42. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Kim BC: FoxO3a mediates transforming growth factor-beta1-induced apoptosis in FaO rat hepatoma cells. BMB Rep. 41:728–732. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Wang S, Chong ZZ, Shang YC and Maiese K: WISP1 neuroprotection requires FoxO3a post-translational modulation with autoregulatory control of SIRT1. Curr Neurovasc Res. 10:54–69. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Liang C, Chen W, Zhi X, et al: Serotonin promotes the proliferation of serum-deprived hepatocellular carcinoma cells via upregulation of FOXO3a. Mol Cancer. 12:142013. View Article : Google Scholar : PubMed/NCBI

26 

Naka K, Hoshii T, Muraguchi T, et al: TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature. 463:676–680. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Yang Y, Jiang H, Gao H, et al: The monoclonal antibody CH12 enhances the sorafenib-mediated growth inhibition of hepatocellular carcinoma xenografts expressing epidermal growth factor receptor variant III. Neoplasia. 14:509–518. 2012.

28 

Chung YW, Kim HK, Kim IY, Yim MB and Chock PB: Dual function of protein kinase C (PKC) in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced manganese superoxide dismutase (MnSOD) expression: activation of CREB and FOXO3a by PKC-alpha phosphorylation and by PKC-mediated inactivation of Akt, respectively. J Biol Chem. 286:29681–29690. 2011.

29 

Kashiwagi A, Fein MJ and Shimada M: Calpain modulates cyclin-dependent kinase inhibitor 1B (p27(Kip1)) in cells of the osteoblast lineage. Calcif Tissue Int. 89:36–42. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Dormond O, Madsen JC and Briscoe DM: The effects of mTOR-Akt interactions on anti-apoptotic signaling in vascular endothelial cells. J Biol Chem. 282:23679–23686. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Davis R, Singh KP, Kurzrock R and Shankar S: Sulforaphane inhibits angiogenesis through activation of FOXO transcription factors. Oncol Rep. 22:1473–1478. 2009.PubMed/NCBI

32 

Wu HH, Wu JY, Cheng YW, et al: cIAP2 upregulated by E6 oncoprotein via epidermal growth factor receptor/phosphatidylinositol 3-kinase/AKT pathway confers resistance to cisplatin in human papillomavirus 16/18-infected lung cancer. Clin Cancer Res. 16:5200–5210. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Kreutzer JN, Ruzzene M and Guerra B: Enhancing chemosensitivity to gemcitabine via RNA interference targeting the catalytic subunits of protein kinase CK2 in human pancreatic cancer cells. BMC Cancer. 10:4402010. View Article : Google Scholar : PubMed/NCBI

34 

Fleischer B, Schulze-Bergkamen H, Schuchmann M, et al: Mcl-1 is an anti-apoptotic factor for human hepatocellular carcinoma. Int J Oncol. 28:25–32. 2006.PubMed/NCBI

35 

He L, Yang X, Cao X, Liu F, Quan M and Cao J: Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma. Oncol Rep. 29:103–108. 2013.PubMed/NCBI

36 

Nayak G and Cooper GM: p53 is a major component of the transcriptional and apoptotic program regulated by PI 3-kinase/Akt/GSK3 signaling. Cell Death Dis. 3:e4002012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang J, Zheng X, Zeng G, Zhou Y and Yuan H: Purified vitexin compound 1 inhibits growth and angiogenesis through activation of FOXO3a by inactivation of Akt in hepatocellular carcinoma. Int J Mol Med 33: 441-448, 2014.
APA
Wang, J., Zheng, X., Zeng, G., Zhou, Y., & Yuan, H. (2014). Purified vitexin compound 1 inhibits growth and angiogenesis through activation of FOXO3a by inactivation of Akt in hepatocellular carcinoma. International Journal of Molecular Medicine, 33, 441-448. https://doi.org/10.3892/ijmm.2013.1587
MLA
Wang, J., Zheng, X., Zeng, G., Zhou, Y., Yuan, H."Purified vitexin compound 1 inhibits growth and angiogenesis through activation of FOXO3a by inactivation of Akt in hepatocellular carcinoma". International Journal of Molecular Medicine 33.2 (2014): 441-448.
Chicago
Wang, J., Zheng, X., Zeng, G., Zhou, Y., Yuan, H."Purified vitexin compound 1 inhibits growth and angiogenesis through activation of FOXO3a by inactivation of Akt in hepatocellular carcinoma". International Journal of Molecular Medicine 33, no. 2 (2014): 441-448. https://doi.org/10.3892/ijmm.2013.1587
Copy and paste a formatted citation
x
Spandidos Publications style
Wang J, Zheng X, Zeng G, Zhou Y and Yuan H: Purified vitexin compound 1 inhibits growth and angiogenesis through activation of FOXO3a by inactivation of Akt in hepatocellular carcinoma. Int J Mol Med 33: 441-448, 2014.
APA
Wang, J., Zheng, X., Zeng, G., Zhou, Y., & Yuan, H. (2014). Purified vitexin compound 1 inhibits growth and angiogenesis through activation of FOXO3a by inactivation of Akt in hepatocellular carcinoma. International Journal of Molecular Medicine, 33, 441-448. https://doi.org/10.3892/ijmm.2013.1587
MLA
Wang, J., Zheng, X., Zeng, G., Zhou, Y., Yuan, H."Purified vitexin compound 1 inhibits growth and angiogenesis through activation of FOXO3a by inactivation of Akt in hepatocellular carcinoma". International Journal of Molecular Medicine 33.2 (2014): 441-448.
Chicago
Wang, J., Zheng, X., Zeng, G., Zhou, Y., Yuan, H."Purified vitexin compound 1 inhibits growth and angiogenesis through activation of FOXO3a by inactivation of Akt in hepatocellular carcinoma". International Journal of Molecular Medicine 33, no. 2 (2014): 441-448. https://doi.org/10.3892/ijmm.2013.1587
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team