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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
January-2016 Volume 13 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
January-2016 Volume 13 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

CK0403, a 9‑aminoacridine, is a potent anti‑cancer agent in human breast cancer cells

  • Authors:
    • Yuan‑Wan Sun
    • Kuen‑Yuan Chen
    • Chul‑Hoon Kwon
    • Kun‑Ming Chen
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Molecular Biology, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA, Department of Surgery, National Taiwan University Hospital, Taipei 8862, Taiwan, R.O.C., Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, New York, NY 11439, USA
  • Pages: 933-938
    |
    Published online on: November 23, 2015
       https://doi.org/10.3892/mmr.2015.4604
  • 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

3‑({4‑[4‑(Acridin‑9‑ylamino)phenylthio]phenyl}(3‑hydroxypropyl)amino)propan‑1‑ol (CK0403) is a sulfur‑containing 9‑anilinoacridine analogue of amsacrine and was found to be more potent than its analogue 2-({4-[4-(acridin-9-ylamino)phenylthio]phenyl}(2‑hydroxyethyl)amino)ethan‑1‑ol (CK0402) and amsacrine in the inhibition of the topoisomerase II‑catalyzed decatenation reaction. A previous study by our group reported that CK0402 was effective against numerous breast cancer cell lines, and the combination of CK0402 with herceptin enhanced its activity in HER2(+) SKBR‑3 cells. In order to identify novel chemotherapeutic agents with enhanced potency, the present study explored the potential of CK0403 in the treatment of breast cancer. First, the growth inhibitory activity of CK0403 in the breast cancer cell lines MCF‑7, MDA‑MB‑231, BT474 and SKBR‑3, as well as in the non‑cancerous MCF‑10A cell line, was examined using a sulforhodamine B assay. The results showed that CK0403 exerted more potent growth inhibitory activity than CK0402 in all of the breast cancer cell lines except MCF‑7. SKBR‑3 and MDA‑MB‑231 were the most sensitive cell lines tested, and the combination of CK0403 with herceptin in HER2(+) SKBR‑3 cells enhanced the growth inhibitory activity of CK0403. Analysis of cell cycle alterations induced by CK0403 in SKBR‑3 cells revealed that, similarly to CK0402, CK0403 induced G2/M‑phase arrest with a decreased S- and G0/G1-phase ratio. In addition, it was shown that CK0403 induced apoptosis more effectively than CK0402 in SKBR‑3 cells. Further analysis of autophagy protein 5 (Atg5) indicated that CK0403 induced more cleaved Atg5 than CK0402 and other chemotherapeutic agents tested. Of note, although still relatively potent, CK0403 exhibited reduced growth inhibitory activity under hypoxic conditions, which can induce autophagy. Collectively, the present results supported that CK0403 is highly potent and more effective than CK0402 against estrogen receptor-negative and HER2‑overexpressing breast cancer cell lines, suggesting its future application for chemotherapy in breast cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Cancer Facts & Figures 2014. American Cancer Society; Atlanta: 2014

2 

Gianni L and Valagussa P: Anthracyclines and early breast cancer: The end of an era? J Clin Oncol. 27:1155–1157. 2009. View Article : Google Scholar : PubMed/NCBI

3 

O'Shaughnessy J: Liposomal anthracyclines for breast cancer: Overview. Oncologist. 8(Suppl 2): S1–S2. 2003. View Article : Google Scholar

4 

Qian BJ, Yan F, Li N, Liu QL, Lin YH, Liu CM, Luo YP, Guo F and Li HZ: MTDH/AEG-1-based DNA vaccine suppresses lung metastasis and enhances chemosensitivity to doxorubicin in breast cancer. Cancer. Immunol Immunother. 60:883–893. 2011. View Article : Google Scholar

5 

Weiss RB: The anthracyclines: Will we ever find a better doxorubicin? Semin Oncol. 19:670–686. 1992.PubMed/NCBI

6 

Carvalho FS, Burgeiro A, Garcia R, Moreno AJ, Carvalho RA and Oliveira PJ: Doxorubicin-induced cardiotoxicity: From bioenergetic failure and cell death to cardiomyopathy. Med Res Rev. 34:106–135. 2014. View Article : Google Scholar

7 

Ng R, Better N and Green MD: Anticancer agents and cardiotoxicity. Semin Oncol. 33:2–14. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Denny WA: DNA-intercalating ligands as anti-cancer drugs: Prospects for future design. Anticancer Drug Des. 4:241–263. 1989.PubMed/NCBI

9 

Minotti G, Menna P, Salvatorelli E, Cairo G and Gianni L: Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 56:185–229. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Baguley BC, Holdaway KM and Fray LM: Design of DNA intercalators to overcome topoisomerase II-mediated multidrug resistance. J Natl Cancer Inst. 82:398–402. 1990. View Article : Google Scholar : PubMed/NCBI

11 

Denny WA: Acridine derivatives as chemotherapeutic agents. Curr Med Chem. 9:1655–1665. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Nelson EM, Tewey KM and Liu LF: Mechanism of antitumor drug action: Poisoning of mammalian DNA topoisomerase II on DNA by 4′-(9-acridinylamino)-methanesulfon-m-anisidide. Proc Natl Acad Sci USA. 81:1361–1365. 1984. View Article : Google Scholar

13 

Chen KM, Sun YW, Tang YW, Sun ZY and Kwon CH: Synthesis and antitumor activity of sulfur-containing 9-anilinoacridines. Mol Pharm. 2:118–128. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Park SK, Kang H and Kwon CH: Caspase-dependent cell death mediates potent cytotoxicity of sulfide derivatives of 9-anilino-acridine. Anticancer Drugs. 19:381–389. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Sun YW, Niu TK, Yang JM, Kwon CH, Chen KY and Chen KM: Potentiation of growth inhibition activity of 2-({4-[4-(acridin-9-ylamino)phenylthio]phenyl}(2-hydroxyethyl) amino) ethan-1-ol (CK0402) by Herceptin in SKBR-3 human breast cancer cells. Exp Ther Med. 1:513–518. 2010.PubMed/NCBI

16 

Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T and Simon HU: Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol. 8:1124–1132. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Baguley BC, Denny WA, Atwell GJ, Finlay GJ, Rewcastle GW, Twigden SJ and Wilson WR: Synthesis, antitumor activity and DNA binding properties of a new derivative of amsacrine, N-5-dimethyl-9-[(2-methoxy-4-methylsulfonylamino) phenylamino]-4-acridinecarboxamide. Cancer Res. 44:3245–3251. 1984.PubMed/NCBI

18 

Fyfe D, Price C, Langley RE, Pagonis C, Houghton J, Osborne L, Woll PJ, Gardner C, Baguley BC and Carmichael J: Cancer Research Campaing Phase I/II Trials Committee: A phase I trial of amsalog (CI-921) administered by intravenous infusion using a 5-day schedule. Cancer Chemother Pharmacol. 47:333–337. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Bacherikov VA, Chou TC, Dong HJ, Zhang X, Chen CH, Lin YW, Tsai TJ, Lee RZ, Liu LF and Su TL: Potent antitumor 9-anilinoacridines bearing an alkylating N-mustard residue on the anilino ring: Synthesis and biological activity. Bioorg Med Chem. 13:3993–4006. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Kapuriya N, Kapuriya K, Zhang X, Chou TC, Kakadiya R, Wu YT, Tsai TH, Chen YT, Lee TC, Shah A, et al: Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage. Bioorg Med Chem. 16:5413–5423. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Su TL, Lin YW, Chou TC, Zhang X, Bacherikov VA, Chen CH, Liu LF and Tsai TJ: Potent antitumor 9-anilinoacridines and acridines bearing an alkylating N-mustard residue on the acridine chromophore: Synthesis and biological activity. J Med Chem. 49:3710–3718. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Chun YS, Adusumilli PS and Fong Y: Employing tumor hypoxia for oncolytic therapy in breast cancer. J Mammary Gland Biol Neoplasia. 10:311–318. 2005. View Article : Google Scholar

23 

Adamski JK, Estlin EJ and Makin GW: The cellular adaptations to hypoxia as novel therapeutic targets in childhood cancer. Cancer Treat Rev. 34:231–246. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Sui X, Chen R, Wang Z, Huang Z, Kong N, Zhang M, Han W, Lou F, Yang J, Zhang Q, et al: Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment. Cell Death Dis. 4:e8382013. View Article : Google Scholar : PubMed/NCBI

25 

Tamura N, Hirano K, Kishino K, Hashimoto K, Amano O, Shimada J and Sakagami H: Analysis of type of cell death induced by topoisomerase inhibitor SN-38 in human oral squamous cell carcinoma cell lines. Anticancer Res. 32:4823–4832. 2012.PubMed/NCBI

26 

Rubinstein AD and Kimchi A: Life in the balance-a mechanistic view of the crosstalk between autophagy and apoptosis. J Cell Sci. 125:5259–5268. 2012. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Sun YW, Chen KY, Kwon CH and Chen KM: CK0403, a 9‑aminoacridine, is a potent anti‑cancer agent in human breast cancer cells. Mol Med Rep 13: 933-938, 2016.
APA
Sun, Y., Chen, K., Kwon, C., & Chen, K. (2016). CK0403, a 9‑aminoacridine, is a potent anti‑cancer agent in human breast cancer cells. Molecular Medicine Reports, 13, 933-938. https://doi.org/10.3892/mmr.2015.4604
MLA
Sun, Y., Chen, K., Kwon, C., Chen, K."CK0403, a 9‑aminoacridine, is a potent anti‑cancer agent in human breast cancer cells". Molecular Medicine Reports 13.1 (2016): 933-938.
Chicago
Sun, Y., Chen, K., Kwon, C., Chen, K."CK0403, a 9‑aminoacridine, is a potent anti‑cancer agent in human breast cancer cells". Molecular Medicine Reports 13, no. 1 (2016): 933-938. https://doi.org/10.3892/mmr.2015.4604
Copy and paste a formatted citation
x
Spandidos Publications style
Sun YW, Chen KY, Kwon CH and Chen KM: CK0403, a 9‑aminoacridine, is a potent anti‑cancer agent in human breast cancer cells. Mol Med Rep 13: 933-938, 2016.
APA
Sun, Y., Chen, K., Kwon, C., & Chen, K. (2016). CK0403, a 9‑aminoacridine, is a potent anti‑cancer agent in human breast cancer cells. Molecular Medicine Reports, 13, 933-938. https://doi.org/10.3892/mmr.2015.4604
MLA
Sun, Y., Chen, K., Kwon, C., Chen, K."CK0403, a 9‑aminoacridine, is a potent anti‑cancer agent in human breast cancer cells". Molecular Medicine Reports 13.1 (2016): 933-938.
Chicago
Sun, Y., Chen, K., Kwon, C., Chen, K."CK0403, a 9‑aminoacridine, is a potent anti‑cancer agent in human breast cancer cells". Molecular Medicine Reports 13, no. 1 (2016): 933-938. https://doi.org/10.3892/mmr.2015.4604
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