Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Jun;67(6):1171–1176. doi: 10.1038/bjc.1993.221

Cellular accumulation of the anticancer agent cisplatin: a review.

D P Gately 1, S B Howell 1
PMCID: PMC1968522  PMID: 8512802

Abstract

Acquired resistance to cisplatin (DDP) is a major clinical problem in the treatment of ovarian, testicular, and head and neck carcinomas; decreased accumulation of DDP is the most consistently observed alteration in resistant cells. It has been postulated that DDP enters the cell by passive diffusion based on the observations that DDP accumulation is proportional to the drug concentration, accumulation is not saturable, and that structural analogs of DDP do not inhibit accumulation. However, recent studies show that DDP accumulation can be specifically stimulated or inhibited by pharmacological agents and the activation of signal transduction pathways. This paper reviews the existing data on the mechanism of DDP accumulation and develops the postulate that some component of transport occurs through a gated ion channel.

Full text

PDF
1171

Selected References

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

  1. Andrews P. A., Howell S. B. Cellular pharmacology of cisplatin: perspectives on mechanisms of acquired resistance. Cancer Cells. 1990 Feb;2(2):35–43. [PubMed] [Google Scholar]
  2. Andrews P. A., Jones J. A., Varki N. M., Howell S. B. Rapid emergence of acquired cis-diamminedichloroplatinum(II) resistance in an in vivo model of human ovarian carcinoma. Cancer Commun. 1990;2(2):93–100. doi: 10.3727/095535490820874641. [DOI] [PubMed] [Google Scholar]
  3. Andrews P. A., Mann S. C., Huynh H. H., Albright K. D. Role of the Na+, K(+)-adenosine triphosphatase in the accumulation of cis-diamminedichloroplatinum(II) in human ovarian carcinoma cells. Cancer Res. 1991 Jul 15;51(14):3677–3681. [PubMed] [Google Scholar]
  4. Andrews P. A., Velury S., Mann S. C., Howell S. B. cis-Diamminedichloroplatinum(II) accumulation in sensitive and resistant human ovarian carcinoma cells. Cancer Res. 1988 Jan 1;48(1):68–73. [PubMed] [Google Scholar]
  5. Basu A., Teicher B. A., Lazo J. S. Involvement of protein kinase C in phorbol ester-induced sensitization of HeLa cells to cis-diamminedichloroplatinum(II). J Biol Chem. 1990 May 25;265(15):8451–8457. [PubMed] [Google Scholar]
  6. Binks S. P., Dobrota M. Kinetics and mechanism of uptake of platinum-based pharmaceuticals by the rat small intestine. Biochem Pharmacol. 1990 Sep 15;40(6):1329–1336. doi: 10.1016/0006-2952(90)90400-f. [DOI] [PubMed] [Google Scholar]
  7. Byfield J. E., Calabro-Jones P. M. Carrier-dependent and carrier-independent transport of anti-cancer alkylating agents. Nature. 1981 Nov 19;294(5838):281–283. doi: 10.1038/294281a0. [DOI] [PubMed] [Google Scholar]
  8. Dornish J. M., Melvik J. E., Pettersen E. O. Reduced cellular uptake of cis-dichlorodiammine-platinum by benzaldehyde. Anticancer Res. 1986 Jul-Aug;6(4):583–588. [PubMed] [Google Scholar]
  9. Dornish J. M., Pettersen E. O., Oftebro R., Melvik J. E. Reduction of cis-dichlorodiammineplatinum-induced cell inactivation by benzaldehyde. Eur J Cancer Clin Oncol. 1984 Oct;20(10):1287–1293. doi: 10.1016/0277-5379(84)90258-x. [DOI] [PubMed] [Google Scholar]
  10. Dornish J. M., Pettersen E. O., Oftebro R. Modifying effect of cinnamaldehyde and cinnamaldehyde derivatives on cell inactivation and cellular uptake of cis-diamminedichloroplatinum(II) in human NHIK 3025 cells. Cancer Res. 1989 Jul 15;49(14):3917–3921. [PubMed] [Google Scholar]
  11. Dornish J. M., Pettersen E. O., Oftebro R. Synergistic cell inactivation by cis-dichlorodiammineplatinum in combination with 1-propargyl-5-chloropyrimidin-2-one. Br J Cancer. 1987 Sep;56(3):273–278. doi: 10.1038/bjc.1987.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dornish J. M., Pettersen E. O. Protection from cis-dichlorodiammineplatinum-induced cell inactivation by aldehydes involves cell membrane amino groups. Cancer Lett. 1985 Dec;29(3):235–243. doi: 10.1016/0304-3835(85)90133-8. [DOI] [PubMed] [Google Scholar]
  13. Gale G. R., Morris C. R., Atkins L. M., Smith A. B. Binding of an antitumor platinum compound to cells as influenced by physical factors and pharmacologically active agents. Cancer Res. 1973 Apr;33(4):813–818. [PubMed] [Google Scholar]
  14. Hromas R. A., North J. A., Burns C. P. Decreased cisplatin uptake by resistant L1210 leukemia cells. Cancer Lett. 1987 Aug;36(2):197–201. doi: 10.1016/0304-3835(87)90091-7. [DOI] [PubMed] [Google Scholar]
  15. Isonishi S., Andrews P. A., Howell S. B. Increased sensitivity to cis-diamminedichloroplatinum(II) in human ovarian carcinoma cells in response to treatment with 12-O-tetradecanoylphorbol 13-acetate. J Biol Chem. 1990 Mar 5;265(7):3623–3627. [PubMed] [Google Scholar]
  16. Isonishi S., Hom D. K., Thiebaut F. B., Mann S. C., Andrews P. A., Basu A., Lazo J. S., Eastman A., Howell S. B. Expression of the c-Ha-ras oncogene in mouse NIH 3T3 cells induces resistance to cisplatin. Cancer Res. 1991 Nov 1;51(21):5903–5909. [PubMed] [Google Scholar]
  17. Kawai K., Kamatani N., Georges E., Ling V. Identification of a membrane glycoprotein overexpressed in murine lymphoma sublines resistant to cis-diamminedichloroplatinum(II). J Biol Chem. 1990 Aug 5;265(22):13137–13142. [PubMed] [Google Scholar]
  18. Kelland L. R., Mistry P., Abel G., Loh S. Y., O'Neill C. F., Murrer B. A., Harrap K. R. Mechanism-related circumvention of acquired cis-diamminedichloroplatinum(II) resistance using two pairs of human ovarian carcinoma cell lines by ammine/amine platinum(IV) dicarboxylates. Cancer Res. 1992 Jul 15;52(14):3857–3864. [PubMed] [Google Scholar]
  19. Kelley S. L., Rozencweig M. Resistance to platinum compounds: mechanisms and beyond. Eur J Cancer Clin Oncol. 1989 Aug;25(8):1135–1140. doi: 10.1016/0277-5379(89)90405-7. [DOI] [PubMed] [Google Scholar]
  20. Kikuchi Y., Iwano I., Miyauchi M., Sasa H., Nagata I., Kuki E. Restorative effects of calmodulin antagonists on reduced cisplatin uptake by cisplatin-resistant human ovarian cancer cells. Gynecol Oncol. 1990 Nov;39(2):199–203. doi: 10.1016/0090-8258(90)90432-k. [DOI] [PubMed] [Google Scholar]
  21. Kraker A. J., Moore C. W. Accumulation of cis-diamminedichloroplatinum(II) and platinum analogues by platinum-resistant murine leukemia cells in vitro. Cancer Res. 1988 Jan 1;48(1):9–13. [PubMed] [Google Scholar]
  22. Mann S. C., Andrews P. A., Howell S. B. Comparison of lipid content, surface membrane fluidity, and temperature dependence of cis-diamminedichloroplatinum(II) accumulation in sensitive and resistant human ovarian carcinoma cells. Anticancer Res. 1988 Nov-Dec;8(6):1211–1215. [PubMed] [Google Scholar]
  23. Mann S. C., Andrews P. A., Howell S. B. Modulation of cis-diamminedichloroplatinum(II) accumulation and sensitivity by forskolin and 3-isobutyl-1-methylxanthine in sensitive and resistant human ovarian carcinoma cells. Int J Cancer. 1991 Jul 30;48(6):866–872. doi: 10.1002/ijc.2910480613. [DOI] [PubMed] [Google Scholar]
  24. Mann S. C., Andrews P. A., Howell S. B. Short-term cis-diamminedichloroplatinum(II) accumulation in sensitive and resistant human ovarian carcinoma cells. Cancer Chemother Pharmacol. 1990;25(4):236–240. doi: 10.1007/BF00684878. [DOI] [PubMed] [Google Scholar]
  25. Melvik J. E., Dornish J. M., Pettersen E. O. The binding of cis-dichlorodiammineplatinum(II) to extracellular and intracellular compounds in relation to drug uptake and cytotoxicity in vitro. Br J Cancer. 1992 Aug;66(2):260–265. doi: 10.1038/bjc.1992.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Melvik J. E., Pettersen E. O., Gordon P. B., Seglen P. O. Increase in cis-dichlorodiammineplatinum (II) cytotoxicity upon reversible electropermeabilization of the plasma membrane in cultured human NHIK 3025 cells. Eur J Cancer Clin Oncol. 1986 Dec;22(12):1523–1530. doi: 10.1016/0277-5379(86)90090-8. [DOI] [PubMed] [Google Scholar]
  27. Melvik J. E., Pettersen E. O. Oxygen- and temperature-dependent cytotoxic and radiosensitizing effects of cis-dichlorodiammineplatinum(II) on human NHIK 3025 cells in vitro. Radiat Res. 1988 Jun;114(3):489–499. [PubMed] [Google Scholar]
  28. Morikage T., Bungo M., Inomata M., Yoshida M., Ohmori T., Fujiwara Y., Nishio K., Saijo N. Reversal of cisplatin resistance with amphotericin B in a non-small cell lung cancer cell line. Jpn J Cancer Res. 1991 Jun;82(6):747–751. doi: 10.1111/j.1349-7006.1991.tb01912.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nicolson M. C., Orr R. M., O'Neill C. F., Harrap K. R. The role of platinum uptake and glutathione levels in L1210 cells sensitive and resistant to cisplatin, tetraplatin or carboplatin. Neoplasma. 1992;39(3):189–195. [PubMed] [Google Scholar]
  30. Ogawa M., Gale G. R., Keirn S. S. Effects of cis-diamminedichloroplatinum (NSC 119875) on murine and human hemopoietic precursor cells. Cancer Res. 1975 Jun;35(6):1398–1401. [PubMed] [Google Scholar]
  31. Perez R. P., Hamilton T. C., Ozols R. F. Resistance to alkylating agents and cisplatin: insights from ovarian carcinoma model systems. Pharmacol Ther. 1990;48(1):19–27. doi: 10.1016/0163-7258(90)90015-t. [DOI] [PubMed] [Google Scholar]
  32. Shionoya S., Lu Y., Scanlon K. J. Properties of amino acid transport systems in K562 cells sensitive and resistant to cis-diamminedichloroplatinum(II). Cancer Res. 1986 Jul;46(7):3445–3448. [PubMed] [Google Scholar]
  33. Timmer-Bosscha H., Hospers G. A., Meijer C., Mulder N. H., Muskiet F. A., Martini I. A., Uges D. R., de Vries E. G. Influence of docosahexaenoic acid on cisplatin resistance in a human small cell lung carcinoma cell line. J Natl Cancer Inst. 1989 Jul 19;81(14):1069–1075. doi: 10.1093/jnci/81.14.1069. [DOI] [PubMed] [Google Scholar]
  34. Timmer-Bosscha H., Mulder N. H., de Vries E. G. Modulation of cis-diamminedichloroplatinum(II) resistance: a review. Br J Cancer. 1992 Aug;66(2):227–238. doi: 10.1038/bjc.1992.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Waud W. R. Differential uptake of cis-diamminedichloroplatinum (II) by sensitive and resistant murine L1210 leukemia cells. Cancer Res. 1987 Dec 15;47(24 Pt 1):6549–6555. [PubMed] [Google Scholar]

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

RESOURCES