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
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
July-2014 Volume 32 Issue 1

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
July-2014 Volume 32 Issue 1

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

2'-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis

  • Authors:
    • Kaijie Wu
    • Zhongyun Ning
    • Jiancheng Zhou
    • Bin Wang
    • Jinhai Fan
    • Jianning Zhu
    • Yang Gao
    • Xinyang Wang
    • Jer-Tsong Hsieh
    • Dalin He
  • View Affiliations / Copyright

    Affiliations: Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
  • Pages: 131-138
    |
    Published online on: May 26, 2014
       https://doi.org/10.3892/or.2014.3218
  • 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

Although there have been advances in therapeutic regimes for metastatic castration-resistant prostate cancer (CRPC), these recent developments have not led to improved cure rates. Thus, more novel agents to prolong patient survival are desired. 2'-Hydroxyflavanone (2HF), a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including prostate cancer (PCa). However, the therapeutic effects of 2HF on tumor growth and its potential mechanisms in CRPC have not been completely elucidated. In the present study, utilizing three different metastatic and androgen-independent PCa cell models (PC-3, DU145 and C4-2), we found that 2HF treatment not only resulted in inhibition of cell proliferation and colony formation in vitro, but also delayed subcutaneous tumor growth in vivo. Mechanistically, besides its known inhibitory effects on aldo‑keto reductase activity and de novo androgen synthesis, 2HF also markedly suppressed AKT phosphorylation, signal transducer and activator of transcription-3 (STAT3) phosphorylation and transactivation subsequently regulating the expression of members of the BCL-2 family (i.e., Mcl-1, Bcl-2 and Bax) and modulating caspase-mediated cell apoptosis. Overall, this study revealed a novel mechanism for 2HF targeting metastatic CRPC, in which inactivation of AKT/STAT3 signaling led to cell apoptosis and growth inhibition.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar

2 

Heidenreich A and Pfister D: Treatment decisions for metastatic castration-resistant prostate cancer progressing after docetaxel chemotherapy: the role of cabazitaxel in the continuum of care. Eur Urol. 62:1201–1204. 2012. View Article : Google Scholar

3 

Beltran H, Beer TM, Carducci MA, et al: New therapies for castration-resistant prostate cancer: efficacy and safety. Eur Urol. 60:279–290. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Mottet N, Bellmunt J, Bolla M, et al: EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 59:572–583. 2011. View Article : Google Scholar

5 

Vitale DC, Piazza C, Melilli B, Drago F and Salomone S: Isoflavones: estrogenic activity, biological effect and bioavailability. Eur J Drug Metab Pharmacokinet. 38:15–25. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Ko CH, Shen SC, Lin HY, et al: Flavanones structure-related inhibition on TPA-induced tumor promotion through suppression of extracellular signal-regulated protein kinases: involvement of prostaglandin E2 in anti-promotive process. J Cell Physiol. 193:93–102. 2002. View Article : Google Scholar

7 

Romagnolo DF and Selmin OI: Flavonoids and cancer prevention: a review of the evidence. J Nutr Gerontol Geriatr. 31:206–238. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Manthey JA, Grohmann K and Guthrie N: Biological properties of citrus flavonoids pertaining to cancer and inflammation. Curr Med Chem. 8:135–153. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Hsiao YC, Kuo WH, Chen PN, et al: Flavanone and 2′-OH flavanone inhibit metastasis of lung cancer cells via down-regulation of proteinases activities and MAPK pathway. Chem Biol Interact. 167:193–206. 2007.

10 

Nagaprashantha LD, Vatsyayan R, Singhal J, et al: 2′-hydroxyflavanone inhibits proliferation, tumor vascularization and promotes normal differentiation in VHL-mutant renal cell carcinoma. Carcinogenesis. 32:568–575. 2011.

11 

Shin SY, Kim JH, Lee JH, Lim Y and Lee YH: 2′-Hydroxyflavanone induces apoptosis through Egr-1 involving expression of Bax, p21, and NAG-1 in colon cancer cells. Mol Nutr Food Res. 56:761–774. 2012.

12 

Wu K, Gore C, Yang L, et al: Slug, a unique androgen-regulated transcription factor, coordinates androgen receptor to facilitate castration resistance in prostate cancer. Mol Endocrinol. 26:1496–1507. 2012. View Article : Google Scholar

13 

Turkson J, Bowman T, Garcia R, Caldenhoven E, De Groot RP and Jove R: Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol Cell Biol. 18:2545–2552. 1998.PubMed/NCBI

14 

Wu K, Fan J, Zhang L, et al: PI3K/Akt to GSK3β/β-catenin signaling cascade coordinates cell colonization for bladder cancer bone metastasis through regulating ZEB1 transcription. Cell Signal. 24:2273–2282. 2012.

15 

Youle RJ and Strasser A: The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 9:47–59. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Majumder PK and Sellers WR: Akt-regulated pathways in prostate cancer. Oncogene. 24:7465–7474. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Nelson EC, Evans CP, Mack PC, Devere-White RW and Lara PN Jr: Inhibition of Akt pathways in the treatment of prostate cancer. Prostate Cancer Prostatic Dis. 10:331–339. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Morgan TM, Koreckij TD and Corey E: Targeted therapy for advanced prostate cancer: inhibition of the PI3K/Akt/mTOR pathway. Curr Cancer Drug Targets. 9:237–249. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Mora LB, Buettner R, Seigne J, et al: Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res. 62:6659–6666. 2002.PubMed/NCBI

20 

Gaya JM, Ahallal Y, Sanchez-Salas R, et al: Current, new and novel therapy for castration-resistant prostate cancer. Expert Rev Anticancer Ther. 13:819–827. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Wu KJ, Zeng J, Zhu GD, et al: Silibinin inhibits prostate cancer invasion, motility and migration by suppressing vimentin and MMP-2 expression. Acta Pharmacol Sin. 30:1162–1168. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Wu K, Zeng J, Li L, et al: Silibinin reverses epithelial-to-mesenchymal transition in metastatic prostate cancer cells by targeting transcription factors. Oncol Rep. 23:1545–1552. 2010.PubMed/NCBI

23 

Zeng J, Sun Y, Wu K, et al: Chemopreventive and chemotherapeutic effects of intravesical silibinin against bladder cancer by acting on mitochondria. Mol Cancer Ther. 10:104–116. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Wu K, Ning Z, Zeng J, et al: Silibinin inhibits β-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial-mesenchymal transition and stemness. Cell Signal. 25:2625–2633. 2013.

25 

Stanbrough M, Bubley GJ, Ross K, et al: Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 66:2815–2825. 2006. View Article : Google Scholar

26 

Yuan X, Cai C, Chen S, Yu Z and Balk SP: Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis. Oncogene. Jun 10–2013.(Epub ahead of print). View Article : Google Scholar

27 

Adeniji AO, Chen M and Penning TM: AKR1C3 as a target in castrate resistant prostate cancer. J Steroid Biochem Mol Biol. 37:136–149. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Ofude M, Mizokami A, Kumaki M, et al: Repression of cell proliferation and androgen receptor activity in prostate cancer cells by 2′-hydroxyflavanone. Anticancer Res. 33:4453–4461. 2013.

29 

Zielinski RR, Eigl BJ and Chi KN: Targeting the apoptosis pathway in prostate cancer. Cancer J. 19:79–89. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Real PJ, Sierra A, De Juan A, Segovia JC, Lopez-Vega JM and Fernandez-Luna JL: Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells. Oncogene. 21:7611–7618. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Zhang D, He D, Xue Y, et al: PrLZ protects prostate cancer cells from apoptosis induced by androgen deprivation via the activation of Stat3/Bcl-2 pathway. Cancer Res. 71:2193–2202. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wu K, Ning Z, Zhou J, Wang B, Fan J, Zhu J, Gao Y, Wang X, Hsieh J, He D, He D, et al: 2'-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis. Oncol Rep 32: 131-138, 2014.
APA
Wu, K., Ning, Z., Zhou, J., Wang, B., Fan, J., Zhu, J. ... He, D. (2014). 2'-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis. Oncology Reports, 32, 131-138. https://doi.org/10.3892/or.2014.3218
MLA
Wu, K., Ning, Z., Zhou, J., Wang, B., Fan, J., Zhu, J., Gao, Y., Wang, X., Hsieh, J., He, D."2'-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis". Oncology Reports 32.1 (2014): 131-138.
Chicago
Wu, K., Ning, Z., Zhou, J., Wang, B., Fan, J., Zhu, J., Gao, Y., Wang, X., Hsieh, J., He, D."2'-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis". Oncology Reports 32, no. 1 (2014): 131-138. https://doi.org/10.3892/or.2014.3218
Copy and paste a formatted citation
x
Spandidos Publications style
Wu K, Ning Z, Zhou J, Wang B, Fan J, Zhu J, Gao Y, Wang X, Hsieh J, He D, He D, et al: 2'-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis. Oncol Rep 32: 131-138, 2014.
APA
Wu, K., Ning, Z., Zhou, J., Wang, B., Fan, J., Zhu, J. ... He, D. (2014). 2'-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis. Oncology Reports, 32, 131-138. https://doi.org/10.3892/or.2014.3218
MLA
Wu, K., Ning, Z., Zhou, J., Wang, B., Fan, J., Zhu, J., Gao, Y., Wang, X., Hsieh, J., He, D."2'-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis". Oncology Reports 32.1 (2014): 131-138.
Chicago
Wu, K., Ning, Z., Zhou, J., Wang, B., Fan, J., Zhu, J., Gao, Y., Wang, X., Hsieh, J., He, D."2'-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis". Oncology Reports 32, no. 1 (2014): 131-138. https://doi.org/10.3892/or.2014.3218
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