Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Feb;71(2):306–310. doi: 10.1038/bjc.1995.61

Selective photodynamic inactivation of a multidrug transporter by a cationic photosensitising agent.

D Kessel 1, K Woodburn 1
PMCID: PMC2033570  PMID: 7841045

Abstract

We have characterised sites of photodamage catalysed by the cationic photosensitiser tetrabromorhodamine 123, using P388 murine leukaemia cells and a subline (P388/ADR) which has a multidrug resistance phenotype and hyperexpresses mdr1 mRNA for P-glycoprotein. Fluorescence emission spectra were consistent with sensitiser localisation in hydrophobic regions of the P388 cell, and in more aqueous loci in P388/ADR. Subsequent irradiation resulted in photodamage to the P388 cells, resulting in loss of viability. In contrast, P388/ADR cells were unaffected except for an irreversible inhibition of P-glycoprotein, leading to enhanced accumulation of daunorubicin and rhodamine 123 and a corresponding increase in daunorubicin cytotoxicity. These results are consistent with the premise that substrates for P-glycoprotein are confined to membrane loci associated with the transporter, and indicate a very limited migration of cytotoxic photo-products in a cellular environment.

Full text

PDF
306

Images in this article

308Figure 2
on p.308

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abou-Khalil S., Abou-Khalil W. H., Planas L., Tapiero H., Lampidis T. J. Interaction of rhodamine 123 with mitochondria isolated from drug-sensitive and -resistant Friend leukemia cells. Biochem Biophys Res Commun. 1985 Mar 29;127(3):1039–1044. doi: 10.1016/s0006-291x(85)80049-8. [DOI] [PubMed] [Google Scholar]
  2. Beck W. T. Mechanisms of multidrug resistance in human tumor cells. The roles of P-glycoprotein, DNA topoisomerase II, and other factors. Cancer Treat Rev. 1990 Dec;17 (Suppl A):11–20. doi: 10.1016/0305-7372(90)90011-4. [DOI] [PubMed] [Google Scholar]
  3. Dellinger M., Pressman B. C., Calderon-Higginson C., Savaraj N., Tapiero H., Kolonias D., Lampidis T. J. Structural requirements of simple organic cations for recognition by multidrug-resistant cells. Cancer Res. 1992 Nov 15;52(22):6385–6389. [PubMed] [Google Scholar]
  4. Germann U. A., Pastan I., Gottesman M. M. P-glycoproteins: mediators of multidrug resistance. Semin Cell Biol. 1993 Feb;4(1):63–76. doi: 10.1006/scel.1993.1008. [DOI] [PubMed] [Google Scholar]
  5. Gottesman M. M., Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem. 1993;62:385–427. doi: 10.1146/annurev.bi.62.070193.002125. [DOI] [PubMed] [Google Scholar]
  6. Henderson B. W., Dougherty T. J. How does photodynamic therapy work? Photochem Photobiol. 1992 Jan;55(1):145–157. doi: 10.1111/j.1751-1097.1992.tb04222.x. [DOI] [PubMed] [Google Scholar]
  7. Johnson R. K., Chitnis M. P., Embrey W. M., Gregory E. B. In vivo characteristics of resistance and cross-resistance of an adriamycin-resistant subline of P388 leukemia. Cancer Treat Rep. 1978 Oct;62(10):1535–1547. [PubMed] [Google Scholar]
  8. Kessel D., Beck W. T., Kukuruga D., Schulz V. Characterization of multidrug resistance by fluorescent dyes. Cancer Res. 1991 Sep 1;51(17):4665–4670. [PubMed] [Google Scholar]
  9. Kessel D., Corbett T. Correlations between anthracycline resistance, drug accumulation and membrane glycoprotein patterns in solid tumors of mice. Cancer Lett. 1985 Sep 15;28(2):187–193. doi: 10.1016/0304-3835(85)90074-6. [DOI] [PubMed] [Google Scholar]
  10. Kessel D. Exploring multidrug resistance using rhodamine 123. Cancer Commun. 1989;1(3):145–149. [PubMed] [Google Scholar]
  11. Kessel D., Hall T. C. Studies on drug transport by normal human leukocytes. Biochem Pharmacol. 1967 Dec;16(12):2395–2403. doi: 10.1016/0006-2952(67)90224-9. [DOI] [PubMed] [Google Scholar]
  12. Kessel D. Sites of photosensitization by derivatives of hematoporphyrin. Photochem Photobiol. 1986 Oct;44(4):489–493. doi: 10.1111/j.1751-1097.1986.tb04697.x. [DOI] [PubMed] [Google Scholar]
  13. Kessel D., Wilberding C. Anthracycline resistance in P388 murine leukemia and its circumvention by calcium antagonists. Cancer Res. 1985 Apr;45(4):1687–1691. [PubMed] [Google Scholar]
  14. Kessel D., Woodburn K., Skalkos D. Impaired accumulation of a cationic photosensitizing agent by a cell line exhibiting multidrug resistance. Photochem Photobiol. 1994 Jul;60(1):61–63. doi: 10.1111/j.1751-1097.1994.tb03943.x. [DOI] [PubMed] [Google Scholar]
  15. Lin C. W., Shulok J. R., Wong Y. K., Schanbacher C. F., Cincotta L., Foley J. W. Photosensitization, uptake, and retention of phenoxazine Nile blue derivatives in human bladder carcinoma cells. Cancer Res. 1991 Feb 15;51(4):1109–1116. [PubMed] [Google Scholar]
  16. Moan J., Berg K. Photochemotherapy of cancer: experimental research. Photochem Photobiol. 1992 Jun;55(6):931–948. doi: 10.1111/j.1751-1097.1992.tb08541.x. [DOI] [PubMed] [Google Scholar]
  17. Moan J., Berg K. The photodegradation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen. Photochem Photobiol. 1991 Apr;53(4):549–553. doi: 10.1111/j.1751-1097.1991.tb03669.x. [DOI] [PubMed] [Google Scholar]
  18. Oseroff A. R., Ohuoha D., Ara G., McAuliffe D., Foley J., Cincotta L. Intramitochondrial dyes allow selective in vitro photolysis of carcinoma cells. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9729–9733. doi: 10.1073/pnas.83.24.9729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Prendergast F. G., Haugland R. P., Callahan P. J. 1-[4-(Trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene: synthesis, fluorescence properties, and use as a fluorescence probe of lipid bilayers. Biochemistry. 1981 Dec 22;20(26):7333–7338. doi: 10.1021/bi00529a002. [DOI] [PubMed] [Google Scholar]
  20. Raviv Y., Pollard H. B., Bruggemann E. P., Pastan I., Gottesman M. M. Photosensitized labeling of a functional multidrug transporter in living drug-resistant tumor cells. J Biol Chem. 1990 Mar 5;265(7):3975–3980. [PubMed] [Google Scholar]
  21. Shea C. R., Chen N., Wimberly J., Hasan T. Rhodamine dyes as potential agents for photochemotherapy of cancer in human bladder carcinoma cells. Cancer Res. 1989 Jul 15;49(14):3961–3965. [PubMed] [Google Scholar]
  22. Shulok J. R., Wade M. H., Lin C. W. Subcellular localization of hematoporphyrin derivative in bladder tumor cells in culture. Photochem Photobiol. 1990 Apr;51(4):451–457. doi: 10.1111/j.1751-1097.1990.tb01736.x. [DOI] [PubMed] [Google Scholar]
  23. Tapiero H., Munck J. N., Fourcade A., Lampidis T. J. Cross-resistance to rhodamine 123 in Adriamycin- and daunorubicin-resistant Friend leukemia cell variants. Cancer Res. 1984 Dec;44(12 Pt 1):5544–5549. [PubMed] [Google Scholar]
  24. Walstad D. L., Brown J. T., Powers S. K. The effect of a chalcogenapyrylium dye with and without photolysis on mitochondrial function in normal and tumor cells. Photochem Photobiol. 1989 Mar;49(3):285–291. doi: 10.1111/j.1751-1097.1989.tb04108.x. [DOI] [PubMed] [Google Scholar]
  25. Zijlstra J. G., de Vries E. G., Mulder N. H. Multifactorial drug resistance in an adriamycin-resistant human small cell lung carcinoma cell line. Cancer Res. 1987 Apr 1;47(7):1780–1784. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES