Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1998 Jun;89(6):673–680. doi: 10.1111/j.1349-7006.1998.tb03270.x

Possibility of Contribution of Nucleoside Transport Systems to Pirarubicin Uptake by HL60 Cells but Not Mononuclear Cells

Kazuki Nagasawa 1, Noriaki Ohnishi 1, Teruyoshi Yokoyama 1,
PMCID: PMC5921878  PMID: 9703366

Abstract

Previously, we reported that pirarubicin (THP), an anthracycline, was taken up, at least in part, by both human leukemic HL60 cells and mononuclear cells (MNCs) via a carrier‐mediated system. In this study, the possibility of a contribution of nucleoside transport systems to the uptake of THP by HL60 cells and MNCs was investigated. The experiments were performed after both types of cells had been pretreated with a metabolic inhibitor, 2, 4‐dinitrophenol, to deplete cellular ATP. In HL60 cells, THP uptake was increased and decreased significantly by treatment with equilibrative nucleoside transport inhibitors, nitrobenzylthioinosine (NBMPR), nitrobenzylthioguanosine and dilazep, in the presence and absence, respectively, of an inwardly directed Na+‐gradient. THP uptake by HL60 cells showed an overshoot in the presence of the gradient, and was decreased by treatment of the cells with monensin, indicating that the uptake partially depended on the Na+‐gradient. In HL60 cells in which equilibrative nucleoside transport was inhibited by NBMPR, THP uptake in the presence of the gradient was inhibited by Na+‐dependent concentrative nucleoside transport inhibitors, but no inhibition was observed in the absence of the gradient. In MNCs, conversely, there was no effect of any equilibrative nucleoside transport inhibitor or the Na+‐gradient on THP uptake. These results suggested that THP was taken up, at least in part, via both equilibrative and concentrative nucleoside transport systems in HL60 cells, but not in MNCs.

Keywords: key words, Pirarubicin, Uptake mechanism, Nucleoside transport system, Human leukemia HL60 cell, Human mononuclear cell

Full Text

The Full Text of this article is available as a PDF (98.8 KB).

REFERENCES

  • 1. ) Nagasawa , K. , Natazuka , T. , Chihara , K. , Kitazawa , F. , Tsumura , A. , Takara , K. , Nomiyama , M. , Ohnishi , N. and Yokoyama , T.Transport mechanism of anthracycline derivatives in human leukemia cell lines: uptake and efflux of pirarubicin in HL60 and pirarubicin‐resistant HL60 cells . Cancer Chemother. Pharmacol. , 37 , 297 – 304 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Nagasawa , K. , Natazuka , T. , Nomiyama , M. , Ohnishi , N. and Yokoyama , T.Transport mechanism of anthracycline derivatives in human leukemia cell lines: uptake and efflux of daunorubicin and doxorubicin in HL60 and its resistant cells and comparison with those of pirarubicin . Biol. Pharm. Bull. , 19 , 100 – 105 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Nagasawa , K. , Tsumura , A. , Nomiyama , M. , Ohnishi , N. and Yokoyama , T.Transport mechanism of pirarubicin in human mononuclear cells . Biol. Pharm. Bull. , 19 , 1203 – 1209 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Plagemann , P. G. W. and Wohlhueter , R. M.Permeation of nucleosides, nucleic acid bases, and nucleotides in animal cells . Curr. Top. Membr. Transp. , 14 , 225 – 329 ( 1980. ). [Google Scholar]
  • 5. ) Plagemann , P. G. W. , Wohlhueter , R. M. and Woffendin , C.Nucleoside and nucleobase transport in animal cells . Biochim. Biophys. Acta , 947 , 405 – 443 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Griffith , D. A. and Jarvis , S. M.Nucleoside and nucleobase transport systems of mammalian cells . Biochim. Biophys. Acta , 1286 , 153 – 181 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Plagemann , P. G. W. and Woffendin , C.Species differences in sensitivity of nucleoside transport in erythrocytes and cultured cells to inhibition by nitrobenzylthioinosine, dipyridamole, dilazep and lidoflazine . Biochim. Biophys. Acta , 969 , 1 – 8 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Crawford , C. R. , Ng , C. Y. C. , Noel , D. and Belt , J. A.Nucleoside transport in L1210 murine leukemia cells . J. Biol. Chem. , 265 , 9732 – 9736 ( 1990. ). [PubMed] [Google Scholar]
  • 9. ) Deckert , J. , Hennemann , A. , Bereznai , B. , Fritze , J. , Vock , R. , Marangos , P. J. and Riederer , P.[3H]Nitrobenzylthioinosine binding sites at the human parietal cortex and erythrocyte adenosine transporter: a comparison . Life Sci. , 55 , 1675 – 1682 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Lee , C. W. , Sokoloski , J. A. , Sartorelli , A. C. and Handschumacher , R. E.Induction of the differentiation of HL‐60 cells by phorbol 12‐myristate 13‐acetate activates a Na+‐dependent uridine‐transport system. Involvement of protein kinase C . Biochem. J. , 274 , 85 – 90 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. ) Sokoloski , J. A. , Sartorelli , A. C. , Handschumacher , R. E. and Lee , C. W.Inhibition by pertussis toxin of the activation of Na+‐dependent uridine transport in dimethyl‐sulphoxide‐induced HL‐60 leukemia cells . Biochem. J. , 280 , 515 – 519 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. ) Goh , L.‐B. , Sokoloski , J. A. , Sartorelli , A. C. and Lee , C.‐W.Enhancement of pertussis‐toxin‐sensitive Na+‐dependent uridine transporter activity in HL‐60 granulocytes by N‐formylmethionyl‐leucyl‐phenylalanine . Biochem. J. , 294 , 693 – 697 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. ) Plagemann , P. G. W. and Aran , J. M.Na+‐dependent, active nucleoside transport in mouse spleen lymphocytes, leukemia cells, fibroblasts and macrophages, but not in equivalent human or pig cells; dipyridamole enhances nucleoside salvage by cells with both active and facilitated transport . Biochim. Biophys. Acta , 1025 , 32 – 42 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Plagemann , P. G. W.Na+‐dependent, concentrative nucleoside transport in rat macrophages. Specificity for natural nucleosides and nucleoside analogues, including dideoxy‐nucleosides, and comparison of nucleoside transport in rat, mouse and human macrophages . Biochem. Pharmacol. , 42 , 247 – 252 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Kusumoto , H. , Maehara , Y. , Anai , H. , Kusumoto , T. and Sugimachi , K.Potentiation of adriamycin cytotoxicity by dipyridamole against HeLa cells in vitro and Sarcoma 180 cells in vivo . Cancer Res. , 48 , 1208 – 1212 ( 1988. ). [PubMed] [Google Scholar]
  • 16. ) Howell , S. B. , Hom , D. , Sanga , R. , Vick , J. S. and Abramson , I. S.Comparison of the synergistic potentiation of etoposide, doxorubicin, and vinblastine cytotoxicity by dipyridamole . Cancer Res. , 49 , 3178 – 3183 ( 1989. ). [PubMed] [Google Scholar]
  • 17. ) Su , J. , Zhen , Y.‐S. , Qi , C.‐Q. and Hu , J.‐L.Antibiotic C3368‐A, a fungus‐derived nucleoside transport inhibitor, potentiates the activity of antitumor drugs . Cancer Chemother. Pharmacol. , 36 , 149 – 154 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Tarasiuk , J. , Foucrier , J. and Garnier‐Suillerot , A.Cell cycle dependent uptake and release of anthracycline by drug‐resistant and drug‐sensitive human leukemic K562 cells . Biochem. Pharmacol. , 45 , 1801 – 1808 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Nagasawa , K. , Ohnishi , N. and Yokoyama , T.Transport mechanisms of idarubicin, an anthracycline derivative, in human leukemia HL60 cells and mononuclear cells, and comparison with those of its analogs . Jpn. J. Cancer Res. , 88 , 750 – 759 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. ) Cai , J. and Lee , C. W.Tamoxifen inhibits nitrobenzylthioinosine‐sensitive equilibrative uridine transport in human MCF‐7 breast cancer cells . Biochem. J. , 320 , 991 – 995 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. ) Suzuki , H. , Sawada , Y. , Sugiyama , Y. , Iga , T. and Hanano , M.Anion exchanger mediates benzylpenicillin transport in rat choroid plexus . J. Pharmacol. Exp. Ther. , 243 , 1147 – 1152 ( 1987. ). [PubMed] [Google Scholar]
  • 22. ) Barcelo , F. , Barcelo , I. , Ferragut , F. A. , Yanovich , S. and Gonzalez‐Ros , J. M.Interaction of anthracyclines with nucleotides and related compounds studied by spectroscopy . Biochim. Biophys. Acta , 884 , 172 – 181 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Drach , D. , Zhao , S. , Drach , J. , Mahadevia , R. , Gattringer , C. , Huber , H. and Andreeff , M.Subpopulations of normal peripheral blood and bone marrow cells express a functional multidrug resistant phenotype . Blood , 80 , 2729 – 2734 ( 1992. ). [PubMed] [Google Scholar]
  • 24. ) Chaudhary , P. M. , Mechetner , E. B. and Roninson , I. B.Expression and activity of the multidrug resistance P‐glycoprotein in human peripheral blood lymphocytes . Blood , 80 , 2735 – 2739 ( 1992. ). [PubMed] [Google Scholar]
  • 25. ) Klimecki , W. T. , Futscher , B. W. , Grogan , T. M. and Dalton , W. S.P‐glycoprotein expression and function in circulating blood cells from normal volunteers . Blood , 83 , 2451 – 2458 ( 1994. ). [PubMed] [Google Scholar]
  • 26. ) Naito , M. , Hoshino , T. , Matsushita , Y. , Hirai , R. and Tsuruo , T.Two types of interaction between P‐glycoprotein and ionophore antibiotics . J. Cell Pharmacol. , 2 , 263 – 267 ( 1991. ). [Google Scholar]
  • 27. ) Dutcher , J. P. , Wiernik , P. H. , Markus , S. , Weinberg , V. , Schiffer , C. A. and Harwood , K. V.Intensive maintenance therapy improves survival in adult acute nonlymphocytic leukemia: an eight‐year follow‐up . Leukemia , 7 , 413 – 419 ( 1988. ). [PubMed] [Google Scholar]
  • 28. ) Yates , J. W. , Glidewell , O. , Wiernik , P. H. , Cooper , M. R. , Steinberg , D. , Dosik , H. , Levy , R. , Hoagland , C. , Henry , P. , Gottleib , A. , Cornell , C. , Berenberg , J. , Hutchison , J. L. , Raich , P. , Nissen , N. , Ellison , R. R. , Frelick , R. , James , G. W. , Falkson , G. , Silver , R. T. , Haurani , F. , Green , M. , Henderson , E. , Leone , L. and Holland , J. F.Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study . Blood , 60 , 454 – 462 ( 1982. ). [PubMed] [Google Scholar]
  • 29. ) Van Sloten , K. , Wiernik , P. H. , Schiffer , C. A. and Schimpff , S. C.Evaluation of levamisole as an adjuvant to chemotherapy for treatment of ANLL . Cancer , 51 , 1576 – 1580 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 30. ) Yates , J. W. , Wallace , H. R. , Ellison , R. R. and Holland , J. F.Cytosine arabinoside (NSC‐63878) and daunorubicin (NSC‐83142) therapy in acute nonlymphocytic leukemia . Cancer Chemother. Rep. , 57 , 485 – 488 ( 1973. ). [PubMed] [Google Scholar]
  • 31. ) Klopman , G. , Srivastava , S. , Kolossvary , I. , Epand , R. F. , Ahmed , N. and Epand , R. M.Structure‐activity study and design of multidrug‐resistant reversal compounds by a computer automated structure evaluation methodology . Cancer Res. , 52 , 4121 – 4129 ( 1992. ). [PubMed] [Google Scholar]
  • 32. ) Goh , L.‐B. , Mack , P. and Lee , C.‐W.Nitrobenzylthioinosine‐binding protein overexpression in human breast, liver, stomach and colorectal tumour tissues . Anticancer Res. , 15 , 2575 – 2580 ( 1995. ). [PubMed] [Google Scholar]
  • 33. ) Deckert , J. , Morgan , P. F. and Marangos , P. J.Adenosine uptake site heterogeneity in the mammalian CNS? Uptake inhibitors as probes and potential neuropharmaceuticals . Life Sci. , 42 , 1331 – 1345 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 34. ) Jones , K. W. and Hammond , J. R.Heterogeneity of [3H]dipyridamole binding to CNS membranes: correlation with [3H]nitrobenzylthioinosine binding and [3H]uridine influx studies . J. Neurochem. , 59 , 1363 – 1371 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 35. ) Williams , E. F.Chronic dipyridamole administration downregulates [3H]nitrobenzylthioinosine binding site affinity in guinea pig kidney but not heart and brain . Life Sci. , 59 , 2051 – 2057 ( 1996. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES