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 Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
July-2015 Volume 47 Issue 1

Full Size Image

Cover Legend PDF

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-2015 Volume 47 Issue 1

Full Size Image

Cover Legend PDF

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

NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity

  • Authors:
    • Hye-In Kim
    • Taelim Kim
    • Ji-Eun Kim
    • Jun Lee
    • Jinyuk Heo
    • Na-Rae Lee
    • Nam-Jung Kim
    • Kyung-Soo Inn
  • View Affiliations / Copyright

    Affiliations: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea, Department of Pharmacy, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea
  • Pages: 280-286
    |
    Published online on: May 12, 2015
       https://doi.org/10.3892/ijo.2015.3002
  • 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

Estrogens act through interactions with estrogen receptors (ERs) to play diverse roles in various pathophysiological conditions. A number of synthetic selective estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, have been developed and used to treat ER-related diseases, including breast cancer and osteoporosis. Here, we identified a novel compound, bis(4-hydroxyphenyl)methanone-O-isopentyl oxime, designated NJK14013, as an ER agonist. NJK14013 activated ER-dependent transcription in a concentration-dependent manner, while suppressing androgen receptor-dependent transcriptional activity. It induced the activation-related phosphorylation of ER and enhanced the transcription of growth regulation by estrogen in breast cancer 1 (GREB1), further supporting its ER-stimulating activity. NJK14013 exerted anti-proliferative effects on various cancer cell lines, including an ER-negative breast cancer cell line, suggesting that it is capable of suppressing the growth of cancer cells independent of its ER-modulating activity. In addition, NJK14013 treatment resulted in significant apoptotic death of MCF7 and Ishikawa cancer cells, but did not induce apoptosis in non-cancer human umbilical vein endothelial cells. Collectively, our findings demonstrate that NJK14013 is a novel SERM that can activate ER-mediated transcription in MCF7 cells and suppress the proliferation of various cancer cells, including breast cancer cells and endometrial cancer cells. These results suggest that NJK14013 has potential as a novel SERM for anticancer or hormone-replacement therapy with reduced risk of carcinogenesis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Mirkin S, Archer DF, Pickar JH and Komm BS: Recent advances help understand and improve the safety of menopausal therapies. Menopause. 22:351–360. 2015. View Article : Google Scholar

2 

Martinkovich S, Shah D, Planey SL and Arnott JA: Selective estrogen receptor modulators: Tissue specificity and clinical utility. Clin Interv Aging. 9:1437–1452. 2014.PubMed/NCBI

3 

Chedraui P, Pérez-López FR, Hidalgo L, Villacreses D, Domínguez A, Escobar GS, Genazzani AR and Simoncini T; Research Group for the Omega Women’s Health Project. Evaluation of the presence and severity of menopausal symptoms among postmenopausal women screened for the metabolic syndrome. Gynecol Endocrinol. Oct 27;2014 (Epub ahead of print). 1–7. 2014.PubMed/NCBI

4 

Ismailoğlu O, Oral B, Gorgulu A, Sutcu R and Demir N: Neuroprotective effects of tamoxifen on experimental spinal cord injury in rats. J Clin Neurosci. 17:1306–1310. 2010. View Article : Google Scholar

5 

Ishihara Y, Itoh K, Ishida A and Yamazaki T: Selective estrogen-receptor modulators suppress microglial activation and neuronal cell death via an estrogen receptor-dependent pathway. J Steroid Biochem Mol Biol. 145:85–93. 2015. View Article : Google Scholar

6 

Pietras RJ: Biologic basis of sequential and combination therapies for hormone-responsive breast cancer. Oncologist. 11:704–717. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Kuss JT, Muss HB, Hoen H and Case LD: Tamoxifen as initial endocrine therapy for metastatic breast cancer: Long term follow-up of two Piedmont Oncology Association (POA) trials. Breast Cancer Res Treat. 42:265–274. 1997. View Article : Google Scholar : PubMed/NCBI

8 

Vogel CL, Johnston MA, Capers C and Braccia D: Toremifene for breast cancer: A review of 20 years of data. Clin Breast Cancer. 14:1–9. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Viedma-Rodríguez R, Baiza-Gutman L, Salamanca-Gómez F, Diaz-Zaragoza M, Martínez-Hernández G, Ruiz Esparza-Garrido R, Velázquez-Flores MA and Arenas-Aranda D: Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer (review). Oncol Rep. 32:3–15. 2014.PubMed/NCBI

10 

Kurebayashi J: Endocrine-resistant breast cancer: Underlying mechanisms and strategies for overcoming resistance. Breast Cancer. 10:112–119. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Decensi A, Maisonneuve P, Rotmensz N, Bettega D, Costa A, Sacchini V, Salvioni A, Travaglini R, Oliviero P, D’Aiuto G, et al; Italian Tamoxifen Study Group. Effect of tamoxifen on venous thromboembolic events in a breast cancer prevention trial. Circulation. 111:650–656. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Bonneterre J, Thürlimann B, Robertson JF, Krzakowski M, Mauriac L, Koralewski P, Vergote I, Webster A, Steinberg M and von Euler M: Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: Results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J Clin Oncol. 18:3748–3757. 2000.PubMed/NCBI

13 

Nagy E, Gajjar KB, Patel II, Taylor S, Martin-Hirsch PL, Stringfellow HF, Martin FL and Phillips DH: MGMT promoter hypermethylation and K-RAS, PTEN and TP53 mutations in tamoxifen-exposed and non-exposed endometrial cancer cases. Br J Cancer. 110:2874–2880. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Avis NE, Crawford SL and McKinlay SM: Psychosocial, behavioral, and health factors related to menopause symptomatology. Womens Health. 3:103–120. 1997.PubMed/NCBI

15 

Buster JE: Transdermal menopausal hormone therapy: Delivery through skin changes the rules. Expert Opin Pharmacother. 11:1489–1499. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Jordan VC: The new biology of estrogen-induced apoptosis applied to treat and prevent breast cancer. Endocr Relat Cancer. 22:R1–R31. 2015. View Article : Google Scholar

17 

Kelly JP, Kaufman DW, Rosenberg L, Kelley K, Cooper SG and Mitchell AA: Use of postmenopausal hormone therapy since the Women’s Health Initiative findings. Pharmacoepidemiol Drug Saf. 14:837–842. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, et al; Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 288:321–333. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, et al: Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: The Women’s Health Initiative Randomized Trial. JAMA. 289:3243–3253. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Craig Jordan V, McDaniel R, Agboke F and Maximov PY: The evolution of nonsteroidal antiestrogens to become selective estrogen receptor modulators. Steroids. 90:3–12. 2014. View Article : Google Scholar : PubMed/NCBI

21 

DeGregorio MW, Zerbe RL and Wurz GT: Ospemifene: A first-in-class, non-hormonal selective estrogen receptor modulator approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy. Steroids. 90:82–93. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Kim HI, Quan FS, Kim JE, Lee NR, Kim HJ, Jo SJ, Lee CM, Jang DS and Inn KS: Inhibition of estrogen signaling through depletion of estrogen receptor alpha by ursolic acid and betulinic acid from Prunella vulgaris var. lilacina. Biochem Biophys Res Commun. 451:282–287. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS and Olson AJ: AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 30:2785–2791. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC and Ferrin TE: UCSF Chimera - a visualization system for exploratory research and analysis. J Comput Chem. 25:1605–1612. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Kaur G, Mahajan MP, Pandey MK, Singh P, Ramisetti SR and Sharma AK: Design, synthesis and evaluation of Ospemifene analogs as anti-breast cancer agents. Eur J Med Chem. 86:211–218. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kim H, Kim T, Kim J, Lee J, Heo J, Lee N, Kim N and Inn K: NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity. Int J Oncol 47: 280-286, 2015.
APA
Kim, H., Kim, T., Kim, J., Lee, J., Heo, J., Lee, N. ... Inn, K. (2015). NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity. International Journal of Oncology, 47, 280-286. https://doi.org/10.3892/ijo.2015.3002
MLA
Kim, H., Kim, T., Kim, J., Lee, J., Heo, J., Lee, N., Kim, N., Inn, K."NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity". International Journal of Oncology 47.1 (2015): 280-286.
Chicago
Kim, H., Kim, T., Kim, J., Lee, J., Heo, J., Lee, N., Kim, N., Inn, K."NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity". International Journal of Oncology 47, no. 1 (2015): 280-286. https://doi.org/10.3892/ijo.2015.3002
Copy and paste a formatted citation
x
Spandidos Publications style
Kim H, Kim T, Kim J, Lee J, Heo J, Lee N, Kim N and Inn K: NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity. Int J Oncol 47: 280-286, 2015.
APA
Kim, H., Kim, T., Kim, J., Lee, J., Heo, J., Lee, N. ... Inn, K. (2015). NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity. International Journal of Oncology, 47, 280-286. https://doi.org/10.3892/ijo.2015.3002
MLA
Kim, H., Kim, T., Kim, J., Lee, J., Heo, J., Lee, N., Kim, N., Inn, K."NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity". International Journal of Oncology 47.1 (2015): 280-286.
Chicago
Kim, H., Kim, T., Kim, J., Lee, J., Heo, J., Lee, N., Kim, N., Inn, K."NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity". International Journal of Oncology 47, no. 1 (2015): 280-286. https://doi.org/10.3892/ijo.2015.3002
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