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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
January-February 2010 Volume 1 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-February 2010 Volume 1 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

The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review)

  • Authors:
    • Yuki Matsui
    • Toshifumi Takeuchi
    • Yuko Kumamoto-Yonezawa
    • Masaharu Takemura
    • Fumio Sugawara
    • Hiromi Yoshida
    • Yoshiyuki Mizushina
  • View Affiliations / Copyright

    Affiliations: Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Hyogo 651-2180, Japan
  • Pages: 19-26
    |
    Published online on: January 1, 2010
       https://doi.org/10.3892/etm_00000004
  • 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

Acetogenins from the Annonaceous plant are a fatty acid-derived natural product. Chemically synthesized natural acetogenins, such as mucocin (compound 1), jimenezin (compound 2), muconin (compound 4), pyranicin (compound 5) and pyragonicin (compound 6) were investigated. Concomitantly, 19-epi jimenezin (compound 3), 10-epi pyragonicin (compound 7) and a γ-lactone (compound 8), which is estimated to be a biosynthetic precursor of acetogenins, were synthesized and investigated. Compounds 5 and 6 strongly inhibited, and compound 7 moderately inhibited the activities of mammalian DNA polymerases (pols), such as replicative pol α and repair/recombination-related pol β and λ, and also inhibited human DNA topoisomerase (topos) I and II activities. On the other hand, compounds 1-4 and 8 did not influence the activities of any pols and topos. Compound 5 was the strongest inhibitor of the pols and topos tested, and the IC50 values were 5.0-9.6 µM, respectively. These compounds also suppressed human cancer cell growth with almost the same tendency as the inhibition of pols and topos. Compound 5 was the strongest suppressor of the proliferation of the promyelocytic leukemia cell line, HL-60, in human cancer cell lines tested with an LD50 value of 9.4 µM, and arrested the cells at G1 phases, indicating that it blocks DNA replication by inhibiting the activity of pols rather than topos. This compound also induced cell apoptosis. The relationship between the three-dimensional molecular structure of acetogenins and these inhibitory activities is discussed. The results suggested that compound 5 is a lead compound of potentially useful cancer chemotherapy agents.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1. 

Rupprecht JK, Hui YH and McLaughlin JL: Annonaceous acetogenins: a review. J Nat Prod. 53:237–278. 1990. View Article : Google Scholar : PubMed/NCBI

2. 

Alali FQ, Liu XX and McLaughlin JL: Annonaceous acetogenins: recent progress. J Nat Prod. 62:504–540. 1999. View Article : Google Scholar : PubMed/NCBI

3. 

Berrnejo A, Figadere B, Zafra-Polo MC, Barrachina I, Estornell E and Cortes D: Acetogenins from Annonaceae: recent progress in isolation, synthesis and mechanisms of action. Nat Prod Rep. 22:269–303. 2005. View Article : Google Scholar : PubMed/NCBI

4. 

Alali FQ, Rogers L, Zhang Y and McLaughlin JL: Unusual bioactive annonaceous acetogenins from Goniothalamus giganteus. Tetrahedron. 54:5833–5844. 1998. View Article : Google Scholar

5. 

Chavez D, Acevedo LA and Mata R: Jimenezin, a novel annonaceous acetogenin from the seeds of Rollinia mucosa containing adjacent tetrahydrofuran-tetrahydropyran ring system. J Nat Prod. 61:419–421. 1998. View Article : Google Scholar

6. 

Shi G, Alfonso D, Fatope MO, Zeng L, Gu ZM, Zhao GX, He K, MacDougal JM and McLaughlin JL: Mucocin: a new annonaceous acetogenin bearing a tetrahydropyran ring. J Am Chem Soc. 117:10409–10410. 1995. View Article : Google Scholar

7. 

Shi G, Kozlowski JF, Schwedler JT, Wood KV, MacDougal JM and McLaughlin JL: Muconin and mucoxin: additional nonclassical bioactive acetogenins from Rollinia mucosa. J Org Chem. 61:7988–7989. 1996. View Article : Google Scholar : PubMed/NCBI

8. 

Kornberg A and Baker TA: Eukaryotic DNA polymerase. DNA replication (2nd edition). Freeman WH and Co. (New York). 197–225. 1992.

9. 

Hubscher U, Maga G and Spadari S: Eukaryotic DNA polymerases. Annu Rev Biochem. 71:133–163. 2002. View Article : Google Scholar

10. 

Bebenek K and Kunkel TA: DNA repair and replication. Advances in Protein Chemistry. 69:Yang W: Elsevier. (San Diego). 137–165. 2004.

11. 

Takata K, Shimizu T, Iwai S and Wood RD: Human DNA polymerase N (POLN) is a low fidelity enzyme capable of error-free bypass of 5S-thymine glycol. J Biol Chem. 281:23445–23455. 2006. View Article : Google Scholar : PubMed/NCBI

12. 

Wang JC: DNA topoisomerases. Annu Rev Biochem. 65:635–692. 1996. View Article : Google Scholar

13. 

Chakraborty AK and Majumder HK: Mode of action of pentavalent antimonials: specific inhibition of type I DNA topoisomerase of Leishmania donovani. Biochem Biophys Res Commun. 152:605–611. 1988. View Article : Google Scholar : PubMed/NCBI

14. 

Liu LF: DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem. 58:351–375. 1989. View Article : Google Scholar : PubMed/NCBI

15. 

Ray S, Hazra B, Mittra B, Das A and Majumder HK: Diospyrin, a bisnaphthoquinone: a novel inhibitor of type I DNA topoisomerase of Leishmania donovani. Mol Pharmacol. 54:994–999. 1998.PubMed/NCBI

16. 

Sakaguchi K, Sugawara F and Mizushina Y: Inhibitors of eukaryotic DNA polymerases. Seikagaku. 74:244–251. 2002.PubMed/NCBI

17. 

Pupo MT, Vieira PC, Fernandes JB and da Silva MFGF: γ-Lactones from Trichilia claussenii. Phytochemistry. 48:307–310. 1998.

18. 

Takahashi S and Nakata T: Total synthesis of an antitumor agent, mucocin, based on the ‘chiron approach’. J Org Chem. 67:5739–5752. 2000.PubMed/NCBI

19. 

Takahashi S, Kubota A and Nakata T: Stereoselective total synthesis of mucocin, an antitumor agent. Angew Chem Int Ed Engl. 41:4751–4754. 2002. View Article : Google Scholar : PubMed/NCBI

20. 

Takahashi S, Maeda K, Hirota S and Nakata T: Total synthesis of a new cytotoxic acetogenin, jimenezin, and the revised structure. Org Lett. 1:2025–2028. 1999. View Article : Google Scholar : PubMed/NCBI

21. 

Takahashi S, Kubota A and Nakata T: Stereoselective total synthesis of muconin. Tetrahedron. 59:1627–1638. 2003. View Article : Google Scholar

22. 

Takahashi S, Kubota A and Nakata T: Total synthesis of a cytotoxic acetogenin, pyranicin. Org Lett. 5:1353–1356. 2003. View Article : Google Scholar : PubMed/NCBI

23. 

Takahashi S, Ogawa N, Koshino H and Nakata T: Total synthesis of the proposed structure for pyragonicin. Org Lett. 7:2783–2786. 2005. View Article : Google Scholar : PubMed/NCBI

24. 

Takahashi S, Hongo H, Ogawa N, Koshino H and Nakata T: Convergent synthesis of pyragonicin. J Org Chem. 71:6305–6308. 2006. View Article : Google Scholar

25. 

Takahashi S, Ogawa N, Sakairi N and Nakata T: Stereoselective synthesis of (2R,3S,4S)-3-hydroxy-4-methyl-2-tetradecyl-4-butanolide starting from 2,5-anhydro-D-mannitol. Tetrahedron. 61:6540–6545. 2005. View Article : Google Scholar

26. 

Mizushina Y, Tanaka N, Yagi H, Kurosawa T, Onoue M, Seto H, Horie T, Aoyagi N, Yamaoka M, Matsukage A, Yoshida S and Sakaguchi K: Fatty acids selectively inhibit eukaryotic DNA polymerase activities in vitro. Biochim Biophys Acta. 1308:256–262. 1996. View Article : Google Scholar : PubMed/NCBI

27. 

Mizushina Y, Yoshida S, Matsukage A and Sakaguchi K: The inhibitory action of fatty acids on DNA polymerase β. Biochim Biophys Acta. 1336:509–521. 1997.

28. 

Ishimaru C, Yonezawa Y, Kuriyama I, Nishida M, Yoshida H and Mizushina Y: Inhibitory effects of cholesterol derivatives on DNA polymerase and topoisomerase activities, and human cancer cell growth. Lipids. 43:373–382. 2008. View Article : Google Scholar : PubMed/NCBI

29. 

Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 65:55–63. 1983. View Article : Google Scholar : PubMed/NCBI

30. 

Murakami-Nakai C, Maeda N, Yonezawa Y, Kuriyama I, Kamisuki S, Takahashi S, Sugawara F, Yoshida H, Sakaguchi K and Mizushina Y: The effects of dehydroaltenusin, a novel mammalian DNA polymerase α inhibitor, on cell proliferation and cell cycle progression. Biochim Biophys Acta. 1674:193–199. 2004.

31. 

Nishida K, Seto M and Ishida R: Different susceptibilities of postmitotic checkpoint-proficient and -deficient Balb/3T3 cells to ICRF-193, a catalytic inhibitor of DNA topoisomerase II. Jpn J Cancer Res. 92:193–202. 2001. View Article : Google Scholar : PubMed/NCBI

32. 

Degli Esposti M: Inhibitors of NADH-ubiquinone reductase: an overview. Biochim Biophys Acta. 1364:222–235. 1998.PubMed/NCBI

33. 

Oberlies NH, Chang CJ and McLaughlin JL: Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells. J Med Chem. 40:2102–2106. 1997. View Article : Google Scholar

34. 

Mizushina Y, Tanaka N, Kitamura A, Tamai K, Ikeda M, Takemura M, Sugawara F, Arai T, Matsukage A, Yoshida S and Sakaguchi K: The inhibitory effect of novel triterpenoid compounds, fomitellic acids, on DNA polymerase β. Biochem J. 330:1325–1332. 1998.PubMed/NCBI

35. 

Tanaka N, Kitamura A, Mizushina Y, Sugawara F and Sakaguchi K: Fomitellic acids, triterpenoid inhibitors of eukaryotic DNA polymerases from a basidiomycete, Fomitella fraxinea. J Nat Prod. 61:193–197. 1998. View Article : Google Scholar : PubMed/NCBI

36. 

Mizushina Y, Ohkubo T, Date T, Yamaguchi T, Saneyoshi M, Sugawara F and Sakaguchi K: Mode analysis of a fatty acid molecule binding to the N-terminal 8-kDa domain of DNA polymerase β. J Biol Chem. 274:25599–25607. 1999.

37. 

Mizushina Y, Sugawara F, Iida A and Sakaguchi K: Structural homology between DNA binding sites of DNA polymerase β and DNA topoisomerase II. J Mol Biol. 304:385–395. 2000.

38. 

Mizushina Y, Iida A, Ohta K, Sugawara F and Sakaguchi K: Novel triterpenoids inhibit both DNA polymerase and DNA topoisomerase. Biochem J. 350:757–763. 2000. View Article : Google Scholar : PubMed/NCBI

39. 

Mizushina Y, Ohkubo T, Sugawara F and Sakaguchi K: Structure of lithocholic acid binding to the N-terminal 8-kDa domain of DNA polymerase β. Biochemistry. 39:12606–12613. 2000.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Matsui Y, Takeuchi T, Kumamoto-Yonezawa Y, Takemura M, Sugawara F, Yoshida H and Mizushina Y: The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) . Exp Ther Med 1: 19-26, 2010.
APA
Matsui, Y., Takeuchi, T., Kumamoto-Yonezawa, Y., Takemura, M., Sugawara, F., Yoshida, H., & Mizushina, Y. (2010). The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) . Experimental and Therapeutic Medicine, 1, 19-26. https://doi.org/10.3892/etm_00000004
MLA
Matsui, Y., Takeuchi, T., Kumamoto-Yonezawa, Y., Takemura, M., Sugawara, F., Yoshida, H., Mizushina, Y."The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) ". Experimental and Therapeutic Medicine 1.1 (2010): 19-26.
Chicago
Matsui, Y., Takeuchi, T., Kumamoto-Yonezawa, Y., Takemura, M., Sugawara, F., Yoshida, H., Mizushina, Y."The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) ". Experimental and Therapeutic Medicine 1, no. 1 (2010): 19-26. https://doi.org/10.3892/etm_00000004
Copy and paste a formatted citation
x
Spandidos Publications style
Matsui Y, Takeuchi T, Kumamoto-Yonezawa Y, Takemura M, Sugawara F, Yoshida H and Mizushina Y: The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) . Exp Ther Med 1: 19-26, 2010.
APA
Matsui, Y., Takeuchi, T., Kumamoto-Yonezawa, Y., Takemura, M., Sugawara, F., Yoshida, H., & Mizushina, Y. (2010). The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) . Experimental and Therapeutic Medicine, 1, 19-26. https://doi.org/10.3892/etm_00000004
MLA
Matsui, Y., Takeuchi, T., Kumamoto-Yonezawa, Y., Takemura, M., Sugawara, F., Yoshida, H., Mizushina, Y."The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) ". Experimental and Therapeutic Medicine 1.1 (2010): 19-26.
Chicago
Matsui, Y., Takeuchi, T., Kumamoto-Yonezawa, Y., Takemura, M., Sugawara, F., Yoshida, H., Mizushina, Y."The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth (Review) ". Experimental and Therapeutic Medicine 1, no. 1 (2010): 19-26. https://doi.org/10.3892/etm_00000004
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