Journal of Cancer Research and Clinical Oncology

, Volume 113, Issue 5, pp 413–416 | Cite as

Antiretroviral activity in a marine red alga: reverse transcriptase inhibition by an aqueous extract of Schizymenia pacifica

  • H. Nakashima
  • Y. Kido
  • N. Kobayashi
  • Y. Motoki
  • M. Neushul
  • N. Yamamoto
Original Papers Experimental Oncology


An aqueous extract from the marine red alga, Schizymenia pacifica has been tested in a cell free system for its effect on reverse transcriptase from avian retrovirus (avian myeloblastosis virus), and mammalian retrovirus (Rauscher murine leukemia virus). The extract inhibited reverse transcriptase from both these retroviruses but showed almost no effect, if any, on the activity of cellular DNA polymerase alpha and RNA polymerase II in vitro. Consequently it is unlikely to have an adverse effect on the growth of cultured cell. The inhibitory activity of the extract was stable over a relatively wide pH range (pH 1–11) and was not lost after pronase digestion. Inhibitory activity of the extract was lost after boiling at 100°C in 0.67 N HCl, and after treatment with 100 mM NaIO4. The active principle in the extract has an apparent molecular weight in excess of 100 000 daltons. This new reverse transcriptase inhibitor is probably a polysaccharide.

Key words

Antiretroviral activity Marine algae Avian myeloblastosis virus Reverse transcriptase 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allaudeen HS, Bertino JR (1978) Inhibition of activities of DNA polymerases α, β, γ and reverse transcriptase of L 1210 cells by phosphonoacetic acid. Biochim Biophys Acta 520:490–497PubMedGoogle Scholar
  2. Baltimore D (1970) RNA-dependent DNA polymerase in virions of RNA tumor viruses. Nature 226:1209–1211PubMedGoogle Scholar
  3. Colon JI, Idoine JB, Brand OM, Costlow RD (1965) Mode of action of an inhibitor from agar on growth and hemagglutination of group A arboviruses. J Bacteriol 90:172–179Google Scholar
  4. Colter JS, Cambell JB (1965) The effect of polyanions and polycations on mengo virus-L cell interaction. Ann NY Acad Sci 130:383–389PubMedGoogle Scholar
  5. De Clercq E (1979) Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses. Cancer Lett 8:9–22CrossRefPubMedGoogle Scholar
  6. De Clercq E (1985) Inhibitors of reverse transcriptase and retrovirus replication. Drug Res 35(I):1007–1008Google Scholar
  7. De Clercq E, Dann O (1980) Diaryl amidine derivatives as oncornaviral DNA polymerase inhibitors. J Med Chem 23:787–795PubMedGoogle Scholar
  8. De Clercq E, Fukui T, Kakikuchi N, Ikehara M, Hattori M, Pfleiderer W (1979) Influence of various 2- and 2′-substituted polyadenylic acids on murine leukemia virus reverse transcriptase. Cancer Lett 7:27–37PubMedGoogle Scholar
  9. DiCioccio RA, Srivastava BIS (1978a) Inhibition of deoxynucleotide-polymerizing enzyme activities of human cells and simian sarcoma virus by heparin. Cancer Res 38:2401–2407PubMedGoogle Scholar
  10. DiCioccio RA, Srivastava BIS (1978b) Structure-activity relationships and specificity of inhibition of DNA polymerase from normal and leukemia cells of man and from simian sarcoma virus by rifamycin derivatives. J Natl Cancer Inst 61:1187–1194PubMedGoogle Scholar
  11. Dieg EF, Ehresmann DW, Hatch MT, Riedlinger DJ (1974) Inhibition of herpes virus replication by marine algae extracts. Antimicrobiol Agents Chemother 6:524–525Google Scholar
  12. Fukui T, De Clercq E (1982) Inhibition of murine leukaemia virus reverse transcriptase by 2-halogenated polyadenylic acids. Biochem J 203:755–760PubMedGoogle Scholar
  13. Harada S, Koyanagi Y, Yamamoto N (1985) Inhibition of human T-lymphotropic virus type-I (HTLV-I)-bearing MT-4 cells with HTLV-III (AIDS virus): Chronological studies of early events. Virology 146:272–281CrossRefPubMedGoogle Scholar
  14. Hoppe O, Levring T, Tanaka Y (1978) Marine algae in pharmaceutical science. W. de Gruter, New YorkGoogle Scholar
  15. Manly KF, Smoler DF, Bromfeld E, Baltimore D (1971) Forms of deoxyribonucleic acid produced by virions of the ribonucleic acid tumor viruses. J Virol 7:106–111PubMedGoogle Scholar
  16. Minowada J, Ohnuma T, Moore GE (1972) Rosette-forming human lymphoid cell lines. I. Establishment and evidence for origin of thymus-derived lymphocytes. J Natl Cancer Inst 49:891–895PubMedGoogle Scholar
  17. Mitsuya H, Broder S (1986) Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus by 2′,3′-dideoxynucleosides. Proc Natl Acad Sci USA 83:1911–1915PubMedGoogle Scholar
  18. Mitsuya H, Weinhold KJ, Furman PA, StClair MH, Lehrman SN, Gallo RC, Bolognesi D, Barry DW, Broder S (1985) 3′-Azido-3′-deoxythymidine (BWA509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci USA 82:7096–7100PubMedGoogle Scholar
  19. Nakashima H, Matsui T, Harada S, Kobayashi N, Matsuda A, Ueda T, Yamamoto N (1986) Inhibition of replication and cytopathic effect of human T cell lymphotropic virus type III/lymphadenopathy-associated virus by 3′-azido-3′-deoxythymidine in vitro. Antimicrobiol Agents Chemother 30:933–937Google Scholar
  20. Rouhandeh H, Sells LL, Chapin M (1966) Effect of L-cystine and sulfated polysaccharides on replication of echovirus type 32 in monkey kidney cells. Proc Soc Exp Biol Med 123:246–249PubMedGoogle Scholar
  21. Rous P (1911) A sarcoma of the folw transmissible by an agent separable from the tumor cells. J Exp Med 13:397–411CrossRefGoogle Scholar
  22. Schulze IT (1964) Reversible inhibition of type 2 dengue virus by agar polysaccharide. Virology 22:79–90CrossRefGoogle Scholar
  23. Sekimizu K, Kobayashi N, Mizuno D, Natori S (1976) Purification of a factor from Ehrlich ascites tumor cells specifically stimulating RNA polymerase II. Biochemistry 15:5064–5070PubMedGoogle Scholar
  24. Shannon WM (1977) Selective inhibition of RNA tumor virus replication in vitro and evaluation of candidate antiviral agents in vivo. Ann NY Acad Sci 284:472–507PubMedGoogle Scholar
  25. Sundquist B, Öberg B (1979) Phosphonoformate inhibits reverse transcriptase. J Gen Virol 45:273–281PubMedGoogle Scholar
  26. Takemoto KK, Fabisch P (1963) Influence of acid polysaccharides on plaque formation by influenza A2 and B viruses. Proc Soc Exp Biol Med 114:811–814PubMedGoogle Scholar
  27. Takemoto KK, Liebhaber H (1961) Virus-polysaccharide interactions I. An agar polysaccharide determines plaque morphology of EMC virus. Virology 14:456–462CrossRefPubMedGoogle Scholar
  28. Temin HM, Mizutani S (1970) RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226:1211–1213PubMedGoogle Scholar
  29. Vogt PK (1977) Genetics of RNA tumor viruses. In: Frankel-Conrat H, Wagner R (eds) Comprehensive virology, vol 9. Plenum Press, New York, pp 341–455Google Scholar
  30. Wright BS, O'Brien PA, Shibley GP, Mayyasi SA, Lasfargues JC (1967) Infection of an established mouse bone marrow cell line (JIS-V9) with Rauscher and Moloney murine leukemia viruses. Cancer Res 27:1672–1675PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • H. Nakashima
    • 1
  • Y. Kido
    • 2
  • N. Kobayashi
    • 1
  • Y. Motoki
    • 2
  • M. Neushul
    • 3
    • 4
  • N. Yamamoto
    • 1
  1. 1.Department of Virology and ParasitologyYamaguchi University School of MedicineYamaguchi 755Japan
  2. 2.Ube Research LaboratoryFujirebio Inc.YamaguchiJapan
  3. 3.Department of Biological SciencesUniversity of California, Santa BarbaraSanta BarbaraUSA
  4. 4.Neushul Mariculture IncorporatedGoletaUSA

Personalised recommendations