Skip to main content
SpringerLink
Log in

Antitumor activity of synthetic alkylphospholipids with or without PAF activity

  • Published:
Lipids

Abstract

1-O-Octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OMe) has been reported to possess definite antitumor activity in vivo. Twenty-two alkyl lysophospholipid analogs were chemically synthesized, and their antitumor activity against mouse experimental tumors (Sarcoma 180, MM46, P388) was examined. Among them, 1-O-octadecyl-2-O-acetoacetyl-rac-glycerol-3-phosphocholine was found to show antitumor activity similar to ET-18-OMe with less acute toxicity.

Intravenous injection of the ET-18-OMe withsn-3 configuration retarded the subcutaneous growth of Sarcoma 180 cells effectively, while the growth inhibition by thesn-1 isomer was much less effective. This stereospecificity was similar to that observed in their activities as platelet-activating factor (PAF) agonists. The acetoacetyl compound, another PAF agonist, showed similar stereospecific antitumor action in vivo. These findings suggest that some alkyl lysophospholipids may activate host cells to a cytostatic stage against tumor cells in vivo through binding to a PAF receptor. Our preliminary results indicated that the responsible cells under these conditions might be primarily immature macrophages present in the bone marrow. No appreciable or even adverse stereospecificity was observed in the different sets of experiments where the activity of ET-18-OMe against MM46 tumor cells in vivo or the direct cytotoxicity against human promyelocytic leukemia HL-60 cells in vitro was examined. Under, some conditions, the antitumor activity of ET-18-OMe in vivo may be revealed through direct cytotoxicity and/or modulation of the host defense system by “nonspecific” mechanisms. Some alkylphospholipids without PAF activity may also show antitumor activity through similar, “nonspecific” mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Munder, P.G., Modolell, M., Bausert, W., Oettgen, H.F., and Westphal, O. (1981) inAugmenting Agents in Cancer Therapy (Hersh, E.M., Chirigos, M.A., and Mastrangelo, M.J., eds.) pp. 441–458, Raven Press, New York.

    Google Scholar 

  2. Andreesen, R., Modolell, M., Weltzien, H.U., Eibl, H., Common, H.H., Loehr, G.W., and Munder, P.G. (1978)Cancer Res. 38, 3894–3899.

    PubMed  CAS  Google Scholar 

  3. Hoffman, D.R., Hajdu, J., and Snyder, F. (1984)Blood 63, 545–552.

    PubMed  CAS  Google Scholar 

  4. Hoffman, D.R., Hoffman, L.H., and Snyder, F. (1986)Cancer Res. 46, 5803–5809.

    PubMed  CAS  Google Scholar 

  5. Helfman, D.M., Barnes, K.C., Kinkade, J.M. Jr., Vogler, W.R., Shoji, M., and Kuo, J.F. (1983)Cancer Res. 43, 2955–2961.

    PubMed  CAS  Google Scholar 

  6. Berdel, W.E., Von Hoff, D.D., Unger, C., Schick, H.D., Fink, U., Reichert, A., Eibl, H., and Rastetter, J. (1986)Lipids 21, 301–304.

    Article  PubMed  CAS  Google Scholar 

  7. Berdel, W.E., Bausert, W.R., Weltzien, H.U., Modolell, M.L., Widmann, K.H., and Munder, P.G. (1980)Eur. J. Cancer 16, 1199–1204.

    PubMed  CAS  Google Scholar 

  8. Benveniste, J., Hensen, P.M., and Cochrane, C.G. (1972)J. Exp. Med. 136, 1356–1377.

    Article  PubMed  CAS  Google Scholar 

  9. Hanahan, D.J. (1986) inAnnual Review of Biochemistry (Richardson, C.C., Boyer, P.D., Dawid, I.B., and Meister, A., eds.) Vol. 55, pp. 483–509, Annual Reviews, Inc., Palo Alto, CA.

    Google Scholar 

  10. Hayashi, H., Kudo, I., Inoue, K., Onozaki, K., Tsushima, S., Nomura, H., and Nojima, S. (1985)J. Biochem. 97, 1737–1745.

    PubMed  CAS  Google Scholar 

  11. Tsushima, S., Yoshioka, Y., Tanida, S., Nomura, H., Nojima, S., and Hozumi, M. (1982)Chem. Pharm. Bull. 30, 3260–3270.

    PubMed  CAS  Google Scholar 

  12. Nojima, S., Nomura, H., and Okutani, T. (1985) Japanese patent application 59-237271.

  13. Kates, M., Chan, T.H., and Stanacev, N.Z. (1963)Biochemistry 2, 394–399.

    Article  CAS  Google Scholar 

  14. Nojima, S. and Nomura, H. (1984) Japanese patent 59-16384.

  15. Nojima, S., Nomura, H., and Tsushima, S. (1985) Japanese patent 60-81193.

  16. Naito, M., Kudo, I., Mukai-Sato, Y., Tsushima, S., Nomura, H., Nojima, S., and Inoue, K. (1987)Cancer Immunol. Immunother. 24, 158–164.

    Article  PubMed  CAS  Google Scholar 

  17. Jerne, N.K., and Nordin, A.A. (1963)Science 140, 405.

    Article  Google Scholar 

  18. Hanahan, D.J., Munder, P.G., Satouchi, K., McManus, L., and Pinckard, R.N. (1981)Biochem. Biophys. Res. Commun. 99, 183–188.

    Article  PubMed  CAS  Google Scholar 

  19. Munder, P.G., Modolell, M., Andressen, R., Weltzien, H.U., and Westphal, O. (1979)Springer Seminar Immunopathol. 2, 187–203.

    Article  CAS  Google Scholar 

  20. Mashino K., Tanaka, Y., Takahashi, K., Inoue, K., and Nojima, S. (1983)J. Biochem. 94, 821–831.

    PubMed  CAS  Google Scholar 

  21. Inarrea, P., Gomez-Cambronero, J., Nieto, M., and Crespo, S. (1984)Eur. J. Pharmacol. 105, 309–315.

    Article  PubMed  CAS  Google Scholar 

  22. Hwang, S-B., Lee, C-S.C., Cheah, M.J., and Shen, T.Y. (1983)Biochemistry 22, 4756–4763.

    Article  PubMed  CAS  Google Scholar 

  23. O’Flaherty, J.T., Surles, J.R., Redman, J., Jacobson, D., Piantadosi, C., and Wykle, R.L. (1986)J. Clin. Invest. 78, 381–388.

    Article  PubMed  CAS  Google Scholar 

  24. Terashita, Z., Imura, Y., and Nishikawa, K. (1985)Biochem. Pharmacol. 34, 1491–1495.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Shoshichi Nojima

    Present address: Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko-machi, 199-01, Kanagawa, Japan

Authors and Affiliations

  1. Department of Health Chemistry, Faculty of Pharmaceutical Sciences, The University of Tokyo, 7-3-1, Hongo, Bunkyoku, 113, Tokyo, Japan

    Ichiro Kudo, Shoshichi Nojima, Hyeun Wook Chang, Ryohei Yanoshita, Hidetoshi Hayashi, Eri Kondo & Keizo Inoue

  2. Central Research Division, Takeda Chemical Industry Ltd., Osaka, Japan

    Hiroaki Nomura

Authors
  1. Ichiro Kudo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shoshichi Nojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyeun Wook Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ryohei Yanoshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hidetoshi Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eri Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroaki Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Keizo Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Kudo, I., Nojima, S., Chang, H.W. et al. Antitumor activity of synthetic alkylphospholipids with or without PAF activity. Lipids 22, 862–867 (1987). https://doi.org/10.1007/BF02535545

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02535545

Keywords

Search

Navigation