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
December-2017 Volume 51 Issue 6

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
December-2017 Volume 51 Issue 6

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 Open Access

5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle

  • Authors:
    • Natasha Borah
    • Shimara Gunawardana
    • Haydee Torres
    • Susan McDonnell
    • Severine Van Slambrouck
  • View Affiliations / Copyright

    Affiliations: Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD 57007, USA, UCD School of Chemical and Bioprocess Engineering, University College Dublin, Belfield Dublin 4, Ireland
    Copyright: © Borah et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1685-1693
    |
    Published online on: October 13, 2017
       https://doi.org/10.3892/ijo.2017.4157
  • 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

Natural components continue to be an important source for the discovery and development of novel anticancer agents. Polymethoxyflavones are a class of flavonoids found in citrus fruits and medicinal plants used in traditional medicine. In the present study, the anticancer activity of the well-known nobiletin (5,6,7,8,3',4'-hexamethoxyflavone) was compared against its less studied structural isomer 5,6,7,3',4',5'-hexamethoxyflavone. These compounds were evaluated on the Hs578T triple-negative breast cancer cell line and its more migratory subclone Hs578Ts(i)8. 5,6,7,3',4',5'-hexamethoxyflavone was found to be less toxic than nobiletin, while a similar growth inhibitory effect was observed after 72 h. Additionally, 5,6,7,3',4',5'-hexamethoxyflavone arrested the cell cycle in the G2/M phase, while no effect was observed on apoptosis or the migratory behavior of these cells. Furthermore, mechanistic studies revealed that the growth inhibition was concomitant with reduced phosphorylation levels of signaling molecules in the MAPK and Akt pathways as well as cell cycle regulators, involved in regulating cell proliferation, survival and cell cycle. In summary, the present study is the first to report on the anticancer activities of 5,6,7,3',4',5'-hexamethoxyflavone and to provide evidence that this flavone could have a greater potential than nobiletin for prevention or treatment of triple- negative breast cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Newman DJ and Cragg GM: Natural products as sources of new drugs over the last 25 years. J Nat Prod. 70:461–477. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Orphan Drug status for alvocidib. Oncology Times. 25–May. 2014, https://doi.org/10.1097/01.COT.0000450374.31680.1d.

3 

Sak K: Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev. 8:122–146. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Walle T: Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass? Semin Cancer Biol. 17:354–362. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Mizuno M, Iinuma M, Ohara M, Tanaka T and Iwamasa M: Chemotaxonomy of the genus Citrus based on polymethoxyflavones. Chem Pharm Bull (Tokyo). 39:945–949. 1991. View Article : Google Scholar

6 

Yenjai C, Prasanphen K, Daodee S, Wongpanich V and Kittakoop P: Bioactive flavonoids from Kaempferia parviflora. Fitoterapia. 75:89–92. 2004. View Article : Google Scholar

7 

Faqueti LG, Brieudes V, Halabalaki M, Skaltsounis AL, Nascimento LF, Barros WM, Santos AR and Biavatti MW: Antinociceptive and anti-inflammatory activities of standardized extract of polymethoxyflavones from Ageratum conyzoides. J Ethnopharmacol. 194:369–377. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Lien LM, Wang MJ, Chen RJ, Chiu HC, Wu JL, Shen MY, Chou DS, Sheu JR, Lin KH and Lu WJ: Nobiletin, a polymethoxylated flavone, inhibits glioma cell growth and migration via arresting cell cycle and suppressing MAPK and Akt pathways. Phytother Res. 30:214–221. 2016. View Article : Google Scholar

9 

Huang H, Li L, Shi W, Liu H, Yang J, Yuan X and Wu L: The multifunctional effects of nobiletin and its metabolites in vivo and in vitro. Evid Based Complement Alternat Med. 2016:29187962016. View Article : Google Scholar :

10 

Chien SY, Hsieh MJ, Chen CJ, Yang SF and Chen MK: Nobiletin inhibits invasion and migration of human nasopharyngeal carcinoma cell lines by involving ERK1/2 and transcriptional inhibition of MMP-2. Expert Opin Ther Targets. 19:307–320. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Surichan S, Androutsopoulos VP, Sifakis S, Koutala E, Tsatsakis A, Arroo RR and Boarder MR: Bioactivation of the citrus flavonoid nobiletin by CYP1 enzymes in MCF7 breast adenocarcinoma cells. Food Chem Toxicol. 50:3320–3328. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Chen C, Ono M, Takeshima M and Nakano S: Antiproliferative and apoptosis-inducing activity of nobiletin against three subtypes of human breast cancer cell lines. Anticancer Res. 34:1785–1792. 2014.PubMed/NCBI

13 

Andreopoulou E, Schweber SJ, Sparano JA and McDaid HM: Therapies for triple negative breast cancer. Expert Opin Pharmacother. 16:983–998. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Adebayo AH, Jig CJ, Zhang YM, He WJ, Zeng GZ, Han HJ, Xu JJ, Akindahunsi AA and Tana NH: A new chromene isolated from Ageratum conyzoides. Nat Prod Commun. 6:1263–1265. 2011.PubMed/NCBI

15 

Itoh T, Ohguchi K, Iinuma M, Nozawa Y and Akao Y: Inhibitory effects of polymethoxy flavones isolated from Citrus reticulate on degranulation in rat basophilic leukemia RBL-2H3: Enhanced inhibition by their combination. Bioorg Med Chem. 16:7592–7598. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Hughes L, Malone C, Chumsri S, Burger AM and McDonnell S: Characterisation of breast cancer cell lines and establishment of a novel isogenic subclone to study migration, invasion and tumourigenicity. Clin Exp Metastasis. 25:549–557. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Romijn JC, Verkoelen CF and Schroeder FH: Application of the MTT assay to human prostate cancer cell lines in vitro: Establishment of test conditions and assessment of hormone-stimulated growth and drug-induced cytostatic and cytotoxic effects. Prostate. 12:99–110. 1988. View Article : Google Scholar : PubMed/NCBI

18 

Rasband WS: ImageJ. U. S. National Institutes of Health; Bethesda, Maryland, USA: https://imagej.nih.gov/ij/. 1997–2016

19 

Payan I, McDonnell S, Torres HM, Steelant WF and Van Slambrouck S: FAK tyrosine 407 organized with integrin αVβ5 in Hs578Ts(i)8 advanced triple-negative breast cancer cells. Int J Oncol. 48:2043–2054. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Mustacchi G and De Laurentiis M: The role of taxanes in triple-negative breast cancer: Literature review. Drug Des Devel Ther. 9:4303–4318. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y and Pietenpol JA: Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 121:2750–2767. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Van Slambrouck S, Parmar VS, Sharma SK, De Bondt B, Foré F, Coopman P, Vanhoecke BW, Boterberg T, Depypere HT, Leclercq G, et al: Tangeretin inhibits extracellular-signal-regulated kinase (ERK) phosphorylation. FEBS Lett. 579:1665–1669. 2005. View Article : Google Scholar : PubMed/NCBI

23 

McConathy J and Owens MJ: Stereochemistry in drug action. Prim Care Companion J Clin Psychiatry. 5:70–73. 2003. View Article : Google Scholar

24 

Baek SH, Kim SM, Nam D, Lee JH and Ahn KS, Choi SH, Kim SH, Shim BS, Chang IM and Ahn KS: Antimetastatic effect of nobiletin through the down-regulation of CXC chemokine receptor type 4 and matrix metallopeptidase-9. Pharm Biol. 50:1210–1218. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Sp N, Kang DY, Joung YH, Park JH, Kim WS, Lee HK, Song KD, Park YM and Yang YM: Nobiletin inhibits angiogenesis by regulating Src/FAK/STAT3-mediated signaling through PXN in ER+ breast cancer cells. Int J Mol Sci. 18:9352017. View Article : Google Scholar

26 

Dong Y, Ji G, Cao A, Shi J, Shi H, Xie J and Wu D: Effects of sinensetin on proliferation and apoptosis of human gastric cancer AGS cells. Zhongguo Zhong Yao Za Zhi. 36:790–794. 2011.In Chinese. PubMed/NCBI

27 

Burkhard K and Shapiro P: Use of inhibitors in the study of MAP kinases. Methods Mol Biol. 661:107–122. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Zannini L, Delia D and Buscemi G: CHK2 kinase in the DNA damage response and beyond. J Mol Cell Biol. 6:442–457. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Singh SV, Herman-Antosiewicz A, Singh AV, Lew KL, Srivastava SK, Kamath R, Brown KD, Zhang L and Baskaran R: Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle 25C. J Biol Chem. 279:25813–25822. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Sancar A, Lindsey-Boltz LA, Unsal-Kaçmaz K and Linn S: Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 73:39–85. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Zhou BB and Bartek J: Targeting the checkpoint kinases: Chemosensitization versus chemoprotection. Nat Rev Cancer. 4:216–225. 2004. View Article : Google Scholar : PubMed/NCBI

32 

DiPaola RS: To arrest or not to G2-M cell-cycle arrest. Clin Cancer Res. 8:3512–3519. 2002.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Borah N, Gunawardana S, Torres H, McDonnell S and Van Slambrouck S: 5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle. Int J Oncol 51: 1685-1693, 2017.
APA
Borah, N., Gunawardana, S., Torres, H., McDonnell, S., & Van Slambrouck, S. (2017). 5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle. International Journal of Oncology, 51, 1685-1693. https://doi.org/10.3892/ijo.2017.4157
MLA
Borah, N., Gunawardana, S., Torres, H., McDonnell, S., Van Slambrouck, S."5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle". International Journal of Oncology 51.6 (2017): 1685-1693.
Chicago
Borah, N., Gunawardana, S., Torres, H., McDonnell, S., Van Slambrouck, S."5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle". International Journal of Oncology 51, no. 6 (2017): 1685-1693. https://doi.org/10.3892/ijo.2017.4157
Copy and paste a formatted citation
x
Spandidos Publications style
Borah N, Gunawardana S, Torres H, McDonnell S and Van Slambrouck S: 5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle. Int J Oncol 51: 1685-1693, 2017.
APA
Borah, N., Gunawardana, S., Torres, H., McDonnell, S., & Van Slambrouck, S. (2017). 5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle. International Journal of Oncology, 51, 1685-1693. https://doi.org/10.3892/ijo.2017.4157
MLA
Borah, N., Gunawardana, S., Torres, H., McDonnell, S., Van Slambrouck, S."5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle". International Journal of Oncology 51.6 (2017): 1685-1693.
Chicago
Borah, N., Gunawardana, S., Torres, H., McDonnell, S., Van Slambrouck, S."5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle". International Journal of Oncology 51, no. 6 (2017): 1685-1693. https://doi.org/10.3892/ijo.2017.4157
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