Skip to main content
Log in

Alteration of membrane lipid biophysical properties and resistance of human lung adenocarcinoma A549 cells to cisplatin

  • Published:
Science in China Series C: Life Sciences Aims and scope Submit manuscript

Abstract

Alterations of membrane lipid biophysical properties of sensitive A549 and resistant A549/DDP cells to the Cis-dichlorodiammine platinum (Cisplatin) were performed by measurements of fluorescence and flow cytometry approaches using fluorescence dyes of DPH, N-AS and Merocyanine 540 (MC 540) respectively. Fatty acids of membrane lipid of the two cell lines were analyzed by gas chromatography. The results indicated clearly that fluorescence polarization (P) of the DPH probe is 0.169 for the sensitive A549 cell and 0.194 for the resistant A549/DDP cells. Statistical analysis showed significant difference between the two cell lines. The polarizations of 2-AS and 7-AS which reflect the fluidity of surface and middle of lipid bilayer are 0.134 and 0.144 for the sensitive A549 cells as well as 0.171 and 0.178 for the resistant A549/DDP cells respectively, but there is no significant difference of the polarization of 12-AS between the two cell lines. This shows that alterations of the membrane fluidity of both cells were mainly located on the surface and middle of the lipid bilayer. In addition, the packing density of phospholipid molecules in the membrane of the two cell lines detected by MC540 probe indicated that lipid packing of A549 cell membranes was looser than that of the A549/DDP cells. And unsaturation degree of plasma membrane fatty acids of the A549/DDP cells was also lower than that of A549 cells. Taken together, it was proposed that the alteration of membrane lipid biophysical state may be involved in the resistance of A549/DDP cells to cisplatin.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Simon, S. M., Schindler, M., Cell biological mechanisms of multidrug resistance in tumors, Proc. Natl. Acad. Sci. USA, 1994, 91: 3497.

    Article  PubMed  CAS  Google Scholar 

  2. Ambudkar, S. V., Dey, S., Hrycyna, C. A. et al., Biochemical, cellular, and pharmacological aspects of the multidrug transporter, Annu. Rev. Pharmacol. Toxicol., 1999, 39: 361.

    Article  PubMed  CAS  Google Scholar 

  3. Dudeja, P. K., Anderson, K. M., Harris, J. S. et al., Reversal of multidrug resistance phenotype by surfactants: Relationship to membrane lipid fluidity, Arch. Biochem. Biophys., 1995, 319 (1): 8309.

    Article  Google Scholar 

  4. Collins, J. M., Scott, R. B., Grogan, W. M., Plasma membrane fluidity gradients of human peripheral blood leukocytes, J. Cell Physiol., 1990, 144: 42.

    Article  PubMed  CAS  Google Scholar 

  5. Collins, J. M., Dominey, R. N., Grogan, W. M., Shape of the fluidity gradient in the plasma membrane of living Hela cells, J. Lipid Res., 1990, 31: 261.

    PubMed  CAS  Google Scholar 

  6. Ashman, R. F., Peckham, D., Alhasan, S. et al., Membrane unpacking and the rapid disposal of apoptotic cells, Immunol. Lett., 1995, 48(3): 159.

    Article  PubMed  CAS  Google Scholar 

  7. Sentjurc, M., Zorec, M., Cemazar, M. et al., Effect of vinblastine on cell membrane fluidity in vinblastine-sensitive and -resistant HeLa cells, Cancer Lett., 1998, 130(1-2): 183.

    Article  PubMed  CAS  Google Scholar 

  8. Regev, R., Assaraf, Y. G., Eytan, G. D. et al., Membrane fluidization by ether, other anesthetics, and certain agents abolishes P-glycoprotein ATPase activity and modulates efflux from multidrug-resistant cells, Eur. J. Biochem., 1999, 259(1-2): 18.

    Article  PubMed  CAS  Google Scholar 

  9. Robert, A. S., Mariamme, S., Katherine, L. S., Altered lipid packing identifies apoptotic thymocytes, Immunol. Lett., 1993, 36: 283.

    Article  Google Scholar 

  10. Lagerberg, J. W., Kallen, K. J., Haest, C. W. et al., Factors affecting the amount and the mode of merocyanine 540 binding to the membrane of human erythrocytes, Biochim. Biophys. Acta, 1995, 1235(2): 428.

    Article  PubMed  Google Scholar 

  11. Stillwell, W., Wassall, S. R., Dumaual, A. C. et al., Use of merocyanine (MC540) in quantifying lipid domains and packing in phospholipid vesicles and tumor cells, Biochem. Biophys. Acta, 1993, 1146(1): 136.

    Article  PubMed  CAS  Google Scholar 

  12. Howlett, N. G., Avery, S. V., Relationship between cadmium sensitivity and degree of plasma membrane fatty acid unsaturation inSaccharomyces cerevisiae, Appl. Microbiol. Biotechnol., 1997, 48(4): 539.

    Article  PubMed  CAS  Google Scholar 

  13. Petriz, J., Oconnor, J. E., Carmona, M. et al., Is Rhodamine-123 an appropriate fluorescent probe to assess P-glycoprotein mediated multidrug resistance in vinblastine-resistant CHO cells? Analytical Cellular Pathology, 1997, 14(3): 129.

    PubMed  CAS  Google Scholar 

  14. Leonce, S., Burbridge, M., Flow cytometry: a useful technique in the study of multidrug resistance, J. Bio. Cell, 1993, 78(1-2): 63.

    Article  CAS  Google Scholar 

  15. Le Moyec, L., Tatoud, R., Degorges, A. et al., Proton nuclear magnetic resonance spectroscopy reveals cellular lipids involved in resistance to Adriamycin and Taxol by the K562 Leukemia cell line, Cancer Res., 1996, 56: 3461.

    PubMed  CAS  Google Scholar 

  16. Callaghan, R., Stafford, A., Epand, R. M., Increased accumulation of drugs in a multidrug resistant cell line by alteration of membrane biophysical properties, Biochim. Biophys. Acta, 1993, 1175(3): 277.

    Article  PubMed  CAS  Google Scholar 

  17. Sinicrope, F. A., Dudeia, P. K., Bissommette, B. M. et al., Modulation of P-glycoprotein-mediated drug transport by alterations in lipid fluidity of rat liver canlicular membrane vesicles, J. Biol. Chem., 1992, 267(35): 24995.

    PubMed  CAS  Google Scholar 

  18. Romsicki, Y., Sharom, F. J., The membrane lipid environment modulates drug interactions with the P-glycoprotein multidrug transporter, Biochemistry, 1999, 38(21): 6887.

    Article  PubMed  CAS  Google Scholar 

  19. Garel, O., Lecureur, V., Guillouzo, A., The P-glycoprotein multidrug transporter, Gen. Pharmacol., 1996, 27(8): 1283.

    Google Scholar 

  20. Aran, J. M., Pastan, I., Gottesman, M. M., Therapeutic strategies involving the multidrug resistance phenotype: the MDR1 gene as target, chemoprotectant, and selectable marker in gene therapy, Adv. Pharmacol., 1999, 46: 1.

    Article  PubMed  CAS  Google Scholar 

  21. Zaman, G. J., Flens, M. J., Vanleusden, M. R. et al., The human multidrug resistance-associated protein (MRP) is a plasma membrane drug efflux pump, Proc. Natl. Acad. Sci. USA, 1994, 91(19): 8822.

    Article  PubMed  CAS  Google Scholar 

  22. Gately, D. P., Howell, S. B., Cellular accumulation of the anticancer agent cisplatin: a review, Br. J. Cancer, 1993, 67: 1171.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Youguo Huang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liang, X., Huang, Y. Alteration of membrane lipid biophysical properties and resistance of human lung adenocarcinoma A549 cells to cisplatin. Sci. China Ser. C.-Life Sci. 44, 25–32 (2001). https://doi.org/10.1007/BF02882069

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02882069

Keywords

Navigation