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. 1986 Dec;83(24):9729–9733. doi: 10.1073/pnas.83.24.9729

Intramitochondrial dyes allow selective in vitro photolysis of carcinoma cells.

A R Oseroff, D Ohuoha, G Ara, D McAuliffe, J Foley, L Cincotta
PMCID: PMC387214  PMID: 3467335

Abstract

Carcinoma cell mitochondria preferentially accumulate and retain certain cationic dyes to a much greater extent than most normal cells. Thus, they can potentially serve as targets for highly selective photochemotherapy. We evaluated 10 rhodamine and cyanine dyes as carcinoma-specific mitochondrial photosensitizers in vitro. The most effective, N,N'-bis(2-ethyl-1,3-dioxolane)kryptocyanine (EDKC), caused marked, light-dependent killing of human bladder, squamous, and colon carcinoma cell lines after 30-min incubations at 1-0.01 microM but was minimally toxic to human keratinocytes and to normal monkey kidney epithelial cells (CV-1). Carcinoma cell phototoxicity was proportional to the amount of dye incorporated by the different cell lines. Selective killing ratios were 70-1000 for 0.1 microM dye and light doses of 100-175 J/cm2 between 680 and 720 nm.

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Selected References

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

  1. Bellnier D. A., Dougherty T. J. Membrane lysis in Chinese hamster ovary cells treated with hemtoporphyrin derivative plus light. Photochem Photobiol. 1982 Jul;36(1):43–47. doi: 10.1111/j.1751-1097.1982.tb04338.x. [DOI] [PubMed] [Google Scholar]
  2. Bernal S. D., Lampidis T. J., McIsaac R. M., Chen L. B. Anticarcinoma activity in vivo of rhodamine 123, a mitochondrial-specific dye. Science. 1983 Oct 14;222(4620):169–172. doi: 10.1126/science.6623064. [DOI] [PubMed] [Google Scholar]
  3. Bernal S. D., Lampidis T. J., Summerhayes I. C., Chen L. B. Rhodamine-123 selectively reduces clonal growth of carcinoma cells in vitro. Science. 1982 Dec 10;218(4577):1117–1119. doi: 10.1126/science.7146897. [DOI] [PubMed] [Google Scholar]
  4. Bustamante C., Stigter D. Intercalation of cationic dyes in the DNA double helix: introductory theory. Biopolymers. 1984 Apr;23(4):629–645. doi: 10.1002/bip.360230405. [DOI] [PubMed] [Google Scholar]
  5. Conover T. E., Schneider R. F. Interaction of certain cationic dyes with the respiratory chain of rat liver mitochondria. J Biol Chem. 1981 Jan 10;256(1):402–408. [PubMed] [Google Scholar]
  6. Dahlman A., Wile A. G., Burns R. G., Mason G. R., Johnson F. M., Berns M. W. Laser photoradiation therapy of cancer. Cancer Res. 1983 Jan;43(1):430–434. [PubMed] [Google Scholar]
  7. Gibson S. L., Hilf R. Photosensitization of mitochondrial cytochrome c oxidase by hematoporphyrin derivative and related porphyrins in vitro and in vivo. Cancer Res. 1983 Sep;43(9):4191–4197. [PubMed] [Google Scholar]
  8. James T. W., Bohman R. Proliferation of mitochondria during the cell cycle of the human cell line (HL-60). J Cell Biol. 1981 May;89(2):256–260. doi: 10.1083/jcb.89.2.256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Johnson L. V., Summerhayes I. C., Chen L. B. Decreased uptake and retention of rhodamine 123 by mitochondria in feline sarcoma virus-transformed mink cells. Cell. 1982 Jan;28(1):7–14. doi: 10.1016/0092-8674(82)90369-5. [DOI] [PubMed] [Google Scholar]
  10. Johnson L. V., Walsh M. L., Bockus B. J., Chen L. B. Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy. J Cell Biol. 1981 Mar;88(3):526–535. doi: 10.1083/jcb.88.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kessel D. Effects of photoactivated porphyrins at the cell surface of leukemia L1210 cells. Biochemistry. 1977 Jul 26;16(15):3443–3449. doi: 10.1021/bi00634a023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lampidis T. J., Bernal S. D., Summerhayes I. C., Chen L. B. Selective toxicity of rhodamine 123 in carcinoma cells in vitro. Cancer Res. 1983 Feb;43(2):716–720. [PubMed] [Google Scholar]
  13. Moan J., Waksvik H., Christensen T. DNA single-strand breaks and sister chromatid exchanges induced by treatment with hematoporphyrin and light or by x-rays in human NHIK 3025 cells. Cancer Res. 1980 Aug;40(8 Pt 1):2915–2918. [PubMed] [Google Scholar]
  14. Nadakavukaren K. K., Nadakavukaren J. J., Chen L. B. Increased rhodamine 123 uptake by carcinoma cells. Cancer Res. 1985 Dec;45(12 Pt 1):6093–6099. [PubMed] [Google Scholar]
  15. Parrish J. A. New concepts in therapeutic photomedicine: photochemistry, optical targeting and the therapeutic window. J Invest Dermatol. 1981 Jul;77(1):45–50. doi: 10.1111/1523-1747.ep12479235. [DOI] [PubMed] [Google Scholar]
  16. Rheinwald J. G., Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975 Nov;6(3):331–343. doi: 10.1016/s0092-8674(75)80001-8. [DOI] [PubMed] [Google Scholar]
  17. Sieber F., Spivak J. L., Sutcliffe A. M. Selective killing of leukemic cells by merocyanine 540-mediated photosensitization. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7584–7587. doi: 10.1073/pnas.81.23.7584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Summerhayes I. C., Lampidis T. J., Bernal S. D., Nadakavukaren J. J., Nadakavukaren K. K., Shepherd E. L., Chen L. B. Unusual retention of rhodamine 123 by mitochondria in muscle and carcinoma cells. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5292–5296. doi: 10.1073/pnas.79.17.5292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Terasaki M., Song J., Wong J. R., Weiss M. J., Chen L. B. Localization of endoplasmic reticulum in living and glutaraldehyde-fixed cells with fluorescent dyes. Cell. 1984 Aug;38(1):101–108. doi: 10.1016/0092-8674(84)90530-0. [DOI] [PubMed] [Google Scholar]
  20. Valinsky J. E., Easton T. G., Reich E. Merocyanine 540 as a fluorescent probe of membranes: selective staining of leukemic and immature hemopoietic cells. Cell. 1978 Mar;13(3):487–499. doi: 10.1016/0092-8674(78)90322-7. [DOI] [PubMed] [Google Scholar]
  21. Wang J., Hogan M., Austin R. H. DNA motions in the nucleosome core particle. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5896–5900. doi: 10.1073/pnas.79.19.5896. [DOI] [PMC free article] [PubMed] [Google Scholar]

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