Skip to main content
SpringerLink
Log in

Membrane lipid alteration: Effect on cellular uptake of mitoxantrone

  • Published:
Lipids

Abstract

We have studied the effect of membrane structural alteration on the cellular association of the anticancer drug mitoxantrone whose uptake is not carrier-mediated. Membrane fatty acids of L1210 cells were modified by incubating the cells with the highly unsaturated docosahexaenoic acid (22∶6), which results in isolated plasma membranes with 37% of the fatty acids as 22∶6, or with the monounsaturated oleic acid (18∶1), which results in 58% of the fatty acids as 18∶1. The rate of uptake by 22∶6-enriched cells during the first min was 62% greater than by those enriched with 18∶1. The higher rate was recorded at 0.5–16 μM, pH 6.6–7.6 and temperatures 10–40 C. The difference in cell-associated drug apparently was not due simply to a change in mitoxantrone solubility as measured by partitioning of the drug in lipophilic-hydrophilic systems containing lipids from the fatty-acid altered cells. We conclude that the type of fatty acids contained in L1210 cell membranes can affect the cell association of mitoxantrone. This effect could be on transmembrane flux or be due to differences in binding of the drug to intracellular structures.

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. Demel, R.A., Guerts van Kessel, W.S.M., and van Deenen, L.L.M. (1972)Biochim. Biophys. Acta 266, 26–40.

    Article  CAS  Google Scholar 

  2. Bruns, C.P., and Spector, A.A. (1987)Lipids 22, 178–184.

    Article  Google Scholar 

  3. Burns, C.P., Haugstad, B.N., and North, J.A. (1987)Biochem. Pharmacol. 36, 857–860.

    Article  PubMed  CAS  Google Scholar 

  4. Zee-Cheng, R.K.Y., and Cheng, C.C. (1978)J. Med. Chem. 21, 291–294.

    Article  PubMed  CAS  Google Scholar 

  5. Murdock, K.C., Child, R.G., Fabio, P.F., Angier, R.B., Wallace, R.E., Burr, F.E., and Citarella, R.V. (1979)J. Med. Chem. 22, 1024–1030.

    Article  PubMed  CAS  Google Scholar 

  6. Kapuscinski, J., Darzynkiewicz, Z., Traganos, F., and Melamed, M.R. (1981)Biochem. Pharm. 30, 231–240.

    Article  PubMed  CAS  Google Scholar 

  7. Bowden, G.T., Roberts, R., Alberts, D.S., Peng, Y., and Garcia, D. (1985)Cancer Res. 45, 4915–4920.

    PubMed  CAS  Google Scholar 

  8. Kapuscinski, J. and Darzynkiewicz, Z. (1986)Proc. Natl. Acad. Sci. USA 83, 6302–6306.

    Article  PubMed  CAS  Google Scholar 

  9. Alberts, D.S., Peng, Y.M., Bowden, G.T., Dalton, W.S., and Mackel, C. (1985)Inv. New Drugs 3, 101–107.

    CAS  Google Scholar 

  10. Guffy, M.M., North, J.A., and Burns, C.P. (1984)Cancer Res. 44, 1863–1866.

    PubMed  CAS  Google Scholar 

  11. Guffy, M.M., Rosenberger, J.A., Simon, I., and Burns, C.P. (1982)Cancer Res. 42, 3625–3630.

    PubMed  CAS  Google Scholar 

  12. Kaduce T.L., Awad, A.B., Fontenelle, L.J. and Spector, A.A. (1977)J. Biol. Chem. 252, 6624–6630.

    PubMed  CAS  Google Scholar 

  13. Burns, C.P., Luttenegger, D.G., Dudley, D.T., Buettner, G.R., and Spector, A.A. (1979)Cancer Res. 39, 1726–1732.

    PubMed  CAS  Google Scholar 

  14. Hyman, B.T., and Spector, A.A. (1982)J. Neurochem. 38, 650–656.

    Article  PubMed  CAS  Google Scholar 

  15. Yorek, M.A., Strom, D.K., and Spector, A.A. (1984)J. Neurochem. 42, 254–261.

    Article  PubMed  CAS  Google Scholar 

  16. Peng, Y.M., Ormberg, D., Alberts, D.S., and Davis, T.P. (1982)J. Chromatogr. 233, 235–247.

    PubMed  CAS  Google Scholar 

  17. Burns, C.P., and Duddley, D.T. (1982)Biochem. Pharmacol. 31, 2116–2119.

    Article  PubMed  CAS  Google Scholar 

  18. Burns, C.P., and North, J.A. (1986),Biochim. Biophys. Acta 888, 10–17.

    Article  PubMed  CAS  Google Scholar 

  19. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. (1951)J. Biol. Chem. 193, 265–275.

    PubMed  CAS  Google Scholar 

  20. Kessel, D. (1979)Biochem. Pharm. 28, 3028–3030.

    Article  PubMed  CAS  Google Scholar 

  21. Duarte-Karim, M., Ruysschaert, J.M., and Hildebrand, J. (1976)Biochem. Biophys. Res. Commun. 71, 658–663.

    Article  PubMed  CAS  Google Scholar 

  22. Tsai, C-M., Chen, K.-Y., and Canellakis, E.S. (1975)Biochim. Biophys. Acta 401, 196–212.

    Article  PubMed  CAS  Google Scholar 

  23. Yang, C.H., Peterson, R.H.F., Sirotnak, F.M., and Chello, P.L. (1979)J. Biol. Chem. 254, 1402–1407.

    PubMed  CAS  Google Scholar 

  24. Avruch, J., and Wallach, D.F.H. (1971)Biochim. Biophys. Acta 233, 334–347.

    Article  PubMed  CAS  Google Scholar 

  25. Folch, J., Lees, M., and Sloane Stanley, G.H. (1957)J. Biol. Chem. 226, 497–509.

    PubMed  CAS  Google Scholar 

  26. Abell, L.L., Levy, B.B., Brodie, B.B., and Kendall, F.E. (1952)J. Biol. Chem. 195, 357–366.

    CAS  Google Scholar 

  27. Morrison, W.R., and Smith, L.M. (1964)J. Lipid Res. 5, 600–608.

    PubMed  CAS  Google Scholar 

  28. Skovsgaard, T., and Nissen, N.I. (1982)Pharmac. Ther. 18, 293–311.

    Article  CAS  Google Scholar 

  29. Siegfried, J.M., Burke, T.G., and Tritton, T.R. (1985)Biochem. Pharm. 34, 593–598.

    Article  PubMed  CAS  Google Scholar 

  30. Johnson, B.A., Cheang, M.S., and Goldenberg, G.J. (1986)Cancer Res., 46, 218–223.

    PubMed  CAS  Google Scholar 

  31. Taylor, R.F., Teague, L.A., and Yesair, D.W. (1981)Cancer Res. 41, 4316–4123.

    PubMed  CAS  Google Scholar 

  32. Schafer, J.A. and Barfuss, D.W. (1986) inMembrane Transport of Antineoplastic Agents (Goldman, I.D., ed.), pp. 1–37, Pergamon Press, Oxford.

    Google Scholar 

  33. Lieb, W.R., and Stein, W.D. (1986)J. Membrane Biol. 92, 111–119.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University of Iowa College of Medicine, 52242, Iowa City, IA

    C. Patrick Burns, Bradley N. Haugstad, Craig J. Mossman, James A. North & Leah M. Ingraham

Authors
  1. C. Patrick Burns
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bradley N. Haugstad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Craig J. Mossman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James A. North
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Leah M. Ingraham
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Burns, C.P., Haugstad, B.N., Mossman, C.J. et al. Membrane lipid alteration: Effect on cellular uptake of mitoxantrone. Lipids 23, 393–397 (1988). https://doi.org/10.1007/BF02535508

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02535508

Keywords

Search

Navigation