Mechanism of sensitization of MDR cancer cells by Pluronic block copolymers: Selective energy depletion

Abstract

This paper, for the first time, demonstrates that exposure of cells to the poly(ethylene oxide)-poly(propylene oxide) block copolymer, Pluronic P85, results in a substantial decrease in ATP levels selectively in MDR cells. Cells expressing high levels of functional P-glycoprotein (MCF-7/ADR, KBv; LLC-MDR1; Caco-2, bovine brain microvessel endothelial cells [BBMECs]) are highly responsive to Pluronic treatment, while cells with low levels of P-glycoprotein expression (MCF-7, KB, LLC-PK1, human umbilical vein endothelial cells [HUVECs] C2C12 myoblasts) are much less responsive to such treatment. Cytotoxicity studies suggest that Pluronic acts as a chemosensitizer and potentiates cytotoxic effects of doxorubicin in MDR cells. The ability of Pluronic to inhibit P-glycoprotein and sensitize MDR cells appears to be a result of ATP depletion. Because many mechanisms of drug resistance are energy dependent, a successful strategy for treating MDR cancer could be based on selective energy depletion in MDR cells. Therefore, the finding of the energy-depleting effects of Pluronic P85, in combination with its sensitization effects is of considerable theoretical and practical significance.

References 26

1. 1.

   Alakhov VYu, Moskaleva EYu, Batrakova E. V., Kabanov A. V. Hypersensitization of multidrug resistant human ovarian carcinoma cells by pluronic P85 block copolymer. Bioconjug Chem. 1996;7(2):209-216.

   Not in our library10.1021/bc950093n

2. 2.

   Altan N., Chen Y., Schindler M., Simon S. M. Defective acidification in human breast tumor cells and implications for chemotherapy. J Exp Med. 1998;187(10):1583-1598.

   Not in our library10.1084/jem.187.10.1583

3. 3.
   Anthracycline antibiotics non-covalently incorporated into the block copolymer micelles: in vivo evaluation of anti-cancer activity · 1996

   No notice
4. 4.

   Batrakova E. V., Han H. Y., Miller D. W., Kabanov A. V. Effects of pluronic P85 unimers and micelles on drug permeability in polarized BBMEC and Caco-2 cells. Pharm Res. 1998;15(10):1525-1532.

   Not in our library10.1023/a:1011942814300

5. 5.

   Batrakova E. V., Miller D. W., Li S., Alakhov V. Y., Kabanov A. V., Elmquist W. F. Pluronic P85 enhances the delivery of digoxin to the brain: in vitro and in vivo studies. J Pharmacol Exp Ther. 2001;296(2):551-557.

   Not in our library

6. 6.

   Benderra Z., Morjani H., Trussardi A., Manfait M. Role of the vacuolar H+-ATPase in daunorubicin distribution in etoposide-resistant MCF7 cells overexpressing the multidrug-resistance associated protein. Int J Oncol. 1998;12(3):711-715.

   Not in our library10.3892/ijo.12.3.711

7. 7.

   Drueckes P., Schinzel R., Palm D. Photometric microtiter assay of inorganic phosphate in the presence of acid-labile organic phosphates. Anal Biochem. 1995;230(1):173-177.

   Not in our library10.1006/abio.1995.1453

8. 8.
   Inhibitory effect of the reversal agents V-104, GF120918 and Pluronic L61 on MDR1 Pgp-, MRP1- and MRP2-mediated transport · 2000

   No notice
9. 9.

   Evers R., Kool M., van Deemter L., Janssen H., Calafat J., Oomen L. C., Paulusma C. C., Oude Elferink R. P., Baas F., Schinkel A. H. Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA. J Clin Invest. 1998;101(7):1310-1319.

   Not in our library10.1172/jci119886

10. 10.

    Evers R., Zaman G. J., van Deemter L., Jansen H., Calafat J., Oomen L. C., Oude Elferink R. P., Borst P., Schinkel A. H. Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells. J Clin Invest. 1996;97(5):1211-1218.

    Not in our library10.1172/jci118535

11. 11.

    Ferrari M., Fornasiero M. C., Isetta A. M. MTT colorimetric assay for testing macrophage cytotoxic activity in vitro. J Immunol Methods. 1990;131(2):165-172.

    Not in our library10.1016/0022-1759(90)90187-z

12. 12.

    Fontaine M., Elmquist W. F., Miller D. W. Use of rhodamine 123 to examine the functional activity of P-glycoprotein in primary cultured brain microvessel endothelial cell monolayers. Life Sci. 1996;59(18):1521-1531.

    Not in our library10.1016/0024-3205(96)00483-3

13. 13.

    Garewal H. S., Ahmann F. R., Schifman R. B., Celniker A. ATP assay: ability to distinguish cytostatic from cytocidal anticancer drug effects. J Natl Cancer Inst. 1986;77(5):1039-1045.

    Not in our library

14. 14.

    Goldstein L. J., Pastan I., Gottesman M. M. Multidrug resistance in human cancer. Crit Rev Oncol Hematol. 1992;12(3):243-253.

    Not in our library10.1016/1040-8428(92)90057-w

15. 15.

    Hayes J. D., Pulford D. J. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol. 1995;30(6):445-600.

    Not in our library10.3109/10409239509083491

16. 16.

    Iwahana M., Utoguchi N., Mayumi T., Goryo M., Okada K. Drug resistance and P-glycoprotein expression in endothelial cells of newly formed capillaries induced by tumors. Anticancer Res. 1998;18(4C):2977-2980.

    Not in our library

17. 17.

    Kaplan O., Jaroszewski J. W., Clarke R., Fairchild C. R., Schoenlein P., Goldenberg S., Gottesman M. M., Cohen J. S. The multidrug resistance phenotype: 31P nuclear magnetic resonance characterization and 2-deoxyglucose toxicity. Cancer Res. 1991;51(6):1638-1644.

    Not in our library

18. 18.

    Kaplan O., Navon G., Lyon R. C., Faustino P. J., Straka E. J., Cohen J. S. Effects of 2-deoxyglucose on drug-sensitive and drug-resistant human breast cancer cells: toxicity and magnetic resonance spectroscopy studies of metabolism. Cancer Res. 1990;50(3):544-551.

    Not in our library

19. 19.

    Kirillova G. P., Mokhova E. N., Dedukhova V. I., Tarakanova A. N., Ivanova V. P., Efremova N. V., Topchieva I. N. The influence of pluronics and their conjugates with proteins on the rate of oxygen consumption by liver mitochondria and thymus lymphocytes. Biotechnol Appl Biochem. 1993;18(Pt 3):329-339.

    Not in our library

20. 20.

    Lee J. S., Paull K., Alvarez M., Hose C., Monks A., Grever M., Fojo A. T., Bates S. E. Rhodamine efflux patterns predict P-glycoprotein substrates in the National Cancer Institute drug screen. Mol Pharmacol. 1994;46(4):627-638.

    Not in our library

21. 21.

    Mansouri A., Henle K. J., Nagle W. A. Multidrug resistance: prospects for clinical management. SAAS Bull Biochem Biotechnol. 1992;5:48-52.

    Not in our library

22. 22.

    Miller D. W., Fontain M., Kolar C., Lawson T. The expression of multidrug resistance-associated protein (MRP) in pancreatic adenocarcinoma cell lines. Cancer Lett. 1996;107(2):301-306.

    Not in our library10.1016/0304-3835(96)04384-4

23. 23.

    Rebbeor J. F., Senior A. E. Effects of cardiovascular drugs on ATPase activity of P-glycoprotein in plasma membranes and in purified reconstituted form. Biochim Biophys Acta. 1998;1369(1):85-93.

    Not in our library10.1016/s0005-2736(97)00185-5

24. 24.

    Shepard R. L., Winter M. A., Hsaio S. C., Pearce H. L., Beck W. T., Dantzig A. H. Effect of modulators on the ATPase activity and vanadate nucleotide trapping of human P-glycoprotein. Biochem Pharmacol. 1998;56(6):719-727.

    Not in our library10.1016/s0006-2952(98)00212-3

25. 25.

    Venne A., Li S., Mandeville R., Kabanov A., Alakhov V. Hypersensitizing effect of pluronic L61 on cytotoxic activity, transport, and subcellular distribution of doxorubicin in multiple drug-resistant cells. Cancer Res. 1996;56(16):3626-3629.

    Not in our library

26. 26.

    Zaman G. J., Lankelma J., van Tellingen O., Beijnen J., Dekker H., Paulusma C., Oude Elferink R. P., Baas F., Borst P. Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein. Proc Natl Acad Sci U S A. 1995;92(17):7690-7694.

    Not in our library10.1073/pnas.92.17.7690

Cited by papers we hold 3

• Novel strategies to prevent the development of multidrug resistance (MDR) in cancer · 2017
  No notice
• Polymeric Micelles, a Promising Drug Delivery System to Enhance Bioavailability of Poorly Water-Soluble Drugs · 2013
  No notice
• Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer · 2004
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.