Skip to main content
SpringerLink
Log in

Etoposide-resistant human colon and lung adenocarcinoma cell lines exhibit sensitivity to homoharringtonine

  • Original Articles
  • Etoposide Resistance, Homoharringtonine Sensitivity
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Human colon (HCT 116/VP48) and lung (A549B/VP29) adenocarcinoma cell lines selected for resistance to etoposide exhibited modified patterns of multidrug resistance (MDR) that included a differential sensitivity to other DNA topoisomerase II inhibitors and to the plant alkaloids homoharringtonine, vinblastine, and vincristine. The resistance and cross-resistance drug phenotype of the A549B/VP29 cell line was different from that of the HCT116/VP48 cell line. The HCT116/VP48 cell line was 50-fold resistant to etoposide and 30-fold resistant to teniposide. The degree of resistance to other DNA topoisomerase II inhibitors was of a lower magnitude: Adriamycin, 9-fold; daunomycin, 3-fold; 4′-[(9-acridinyl)-amino]-methanesulfone-m-anisidide (m-AMSA), 3-fold;, and actinomycin D, 6-fold. The HCT 116/VP48 cell line exhibited a 7-fold resistance to vincristine and a 2-fold resistance to vinblastine but was sensitive to homoharringtohine. The A549B/VP29 cell line was 5-fold resistant to etoposide and 2-fold resistant to teniposide. The A549B/VP29 cell line exhibited a 2-fold resistance to Adriamycin but was sensitive to daunomycin and showed a 3-fold resistance to m-AMSA. This cell line was sensitive to actinomycin D. The A549B/VP29 cell line was 2-fold resistant to vinblastine and sensitive to homoharringtonine. Both cell lines (HCT116/VP48 and A549/VP29) exhibited no amplification of the humanmdrl DNA sequence, the 4.3-kb P-glycoprotein transcript, or the membrane P-glycoprotein. The sensitivity of cells exhibiting an MDR phenotype not mediated by P-glycoprotein suggests a potential use for homoharringtonine in treating tumors with this type of drug resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Abromowitch M, Bowman WP, Ochs J, Rivera G (1986) Etoposide (VP-16) with prednisone and vincristine for the treatment of refractory acute lymphoblastic leukemia. J Clin Oncol 3:789

    Google Scholar 

  2. Annual report to the Food and Drug Administration (1986) Homoharringtonine NSC 141633, IND 19125. Division of Cancer Treatment, NCl, Bethesda, Maryland

  3. Brattain MG, Brattain DE, Fine WD Khaled FM, Marks ME, Arcolano LA, Danbury BH (1981) Initiation and characterization of cultures of human colonic carcinoma with different biological characteristics utilizing feeder layers of confluent fibroblasts. Oncodev Biol Med 2:355

    Google Scholar 

  4. Chabner BA, Fojo A (1989) Multidrug resistance: P-glycoprotein and its allies-the elusive foes. J Natl Cancer Inst 81:910

    Google Scholar 

  5. Chou TC, Schmid FA, Feinberg A, Philips FS, Han J (1983) Uptake, initial effects, and chemotherapeutic efficacy of harringtonine in murine leukemic cells sensitive and resistant to vincristine and other chemotherapeutic agents. Cancer Res 43:3074

    Google Scholar 

  6. Endicott JA, Ling V (1989) The biochemistry of P-glycoprotein mediated multidrug resistance. Annu Rev Biochem 58:137

    Google Scholar 

  7. Feramisco JR, Helfman DM, Smart JE, Burridge K, Thomas, GP (1982) Coexistence of vinculin-like protein of high molecular weight in smooth muscle. J Biol Chem 257:11024

    Google Scholar 

  8. Fresno M, Jimenez A, Vazquez D (1977) Inhibition of translation in eukaryotic systems by harringtonine. Eur J Biochem 72:323

    Google Scholar 

  9. Hsieh T-S (1983) Purification and properties of type II DNA topoisomerase from embryos ofDrosophila melanogaster. In: Wu R (ed) Methods in enzymology, vol 100. Academic Press, London, p 161

    Google Scholar 

  10. Huang MT (1975) Harringtonine, an inhibitor of protein synthesis. Mol Pharmacol 11:511

    Google Scholar 

  11. Jackson DV, Long TR, Trakey TF, Morgan TN (1984) Synergistic antitumor activity of vincristine and VP-16-213. Cancer Chemother Pharmacol 13:176

    Google Scholar 

  12. Jackson D, Long T, Rice D, Capizzi R (1985) Synergistic antitumor activity of VP-16-213 follored by vincristine. Proc Am Assoc Cancer Res 26:236

    Google Scholar 

  13. Liu LF (1989) DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem 58:351

    Google Scholar 

  14. Liu LF, Davis JD, Calender R (1981) Novel topologically knotted DNA from bacteriophage P4 capsids: studies with DNA topoisomerases. Nucleic Acids Res 9:3979

    Google Scholar 

  15. Long BH (1987) Structure-activity relationship of podophyllin congeners that inhibit topoisomer II. In: Potmesil M, Ross WE (eds) First conference on DNA topoisomerases in cancer chemotherapy. (National Cancer Institute Monograph series, vol 4) National Cancer Institute, Bethesda, MD (USA), pp 123–127

    Google Scholar 

  16. Long BH, Musial ST, Brattain MG (1985) Single-and double-strand DNA breakage and repair in human lung adenocarcinoma cells exposed to etoposide and teniposide. Cancer Res 45:3106

    Google Scholar 

  17. Long BH, Musial ST, Brattain MG (1986) DNA breakage in human lung carcinoma cells and nuclei that are naturally sensitive or resistant to etoposide and teniposide. Cancer Res 46:3809

    Google Scholar 

  18. Long BH, Wang L, Lorico A, Wang RCC, Brattain MG, Easazza AM (1991) Mechanisms of resistance to etoposide and teniposide in acquired resistant human colon and lung carcinoma cell lines. Cancer Res 51:5275

    Google Scholar 

  19. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurements with the folin phenol reagent. J Biol Chem 193:265

    Google Scholar 

  20. Maniatias T, Fritsch EF, Sambrook J (1982) Molecular cloning, a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, p 326

    Google Scholar 

  21. Neidhart JA, Young DC, Kraut E, Howinstein B, Metz EN (1986) Phase I trial of homoharringtonine administered by prolonged continuous infusion. Cancer Res 46:967

    Google Scholar 

  22. Ohnuma T, Holland JF (1985) Homoharringtonine as a new antileukemic agent. J Clin Oncol 3:604

    Google Scholar 

  23. Rivera G, Bowman WP, Murphy SB, Dahl GV, Aur RJ, Kalwinsky DK, Wood A, Stagner S, Avery TL (1982) VM-26 with prednisone and vincristine for treatment of refractory acute lymphocytic leukemia. Med Pediatr Oncol 10:439

    Google Scholar 

  24. Roninson IB, Chin JE, Choi K, Gros P, Housman DE, Fojo A, Shen D, Gottesman, MM, Pastan I (1986) Isolation of humanmdr DNA sequences amplified in multidrug-resistant KB carcinoma cells. Proc Natl Acad Sci USA 83:4532

    Google Scholar 

  25. Samuels BL, Murray JL, Cohen MB, Safa AR, Sinha BK, Townsend AJ, Beckett MA, Weichselbaum RR (1991) Increased glutathione peroxidase activity in a human sarcoma cell line with inherent doxorubicin resistance. Cancer Res 51:521

    Google Scholar 

  26. Shoemaker R, Wolpert-DeFilippes M, Plowman J, Abbott B, Venditti J, Trader M, Griswold D, Gerlach J, Ling V (1986) Photropic resistance and drug development. In: Hall TC (ed) Progress in clinical and biological research, vol 223. Cancer drug resistance. Alan R. Liss, New York, p 143

    Google Scholar 

  27. Sullivan DM, Latham MD, Ross WE (1987) Proliferation-dependent topoisomerase II content as a determinant of antineoplastic drug action in human, mouse, and Chinese hamster ovary cells. Cancer Res 47:3973

    Google Scholar 

  28. Takemura Y, Ohnuma T, Chou T-C, Okano T, Holland JF (1985) Biologic and pharmacologic effects of harringtonine on human leukemia-lymphoma cells. Cancer Chemother Pharmacol 14:206

    Google Scholar 

  29. Tebbi CK, Chervinsky D (1986) The effects of homoharringtonine (HTT) on mouse C-1300 neuroblastoma in vitro and in vivo., Proc Am Assoc Cancer Res 27:274

    Google Scholar 

  30. Tebbi CK, Chervinsky D, Baker RM (1991) Modulation of drug resistance in homoharringyonine-resistant C-1300 neuroblastoma cells with cyclosporine A and dipyridamole. J Cell Physiol 148:464

    Google Scholar 

  31. Thomas PS (1983) Hybridization of denatured RNA transferred or blotted to nitrocellulose paper. In: Wu R (ed) Methods in enzymology, vol 100. Academic Press. London, p 255

    Google Scholar 

  32. Towbin H, Stächelin T, Gordon J (1979), Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose: procedure and some applications. Proc Natl Acad Sci USA 76:4350

    Google Scholar 

  33. Warrell RP Jr, Coonley CJ, Gee TS (1985) Homoharringtonine, an effective new drug for remission induction in refractory nonlymphoblastic leukemia. J Clin Oncol 3:617

    Google Scholar 

  34. Wilkoff LJ, Dulmadge EA, Laster WR Jr, Griswold DP Jr (1989) Effect of homoharringtonine on the viability of murine leukemia P388 cells resistant to either Adriamycin, vincristine, or 1-β-d-arabinofuranosyl cytosine. Cancer Chemother Pharmacol 23:145

    Google Scholar 

  35. Wilson JKV, Long BH, Marks ME, Brattain DE, Wiley JE, Brattain MG (1984) Mitomycin C resistance in a human colon carcinoma cell line associated with cell surface protein alterations. Cancer Res 44:5880

    Google Scholar 

  36. Wolverton JS, Danks MK, Schmidt CA, Beck WT (1989) Genetic characterization of the multidrug-resistant phenotype of VM-26-resistant human leukemic cells. Cancer Res 49:2422

    Google Scholar 

  37. Yalowich JC (1987) Effects of microtubule inhibitors on etoposide accumulation and DNA damage in human K562 cells in vitro. Cancer Res 47:1010

    Google Scholar 

  38. Zwelling LA, Slovak ML, Doroshow JH, Hinds M, Chan D, Parker E, Mayes J, Sie KL, Meltzer PS, Trent JM (1990) HT1080/DR4: a P-glycoprotein-negative human fibrosarcoma cell line exhibiting resistance to topisomerase II-reactive drugs despite the presence of a drug-sensitive topoisomerase II. J Natl Cancer Inst 82:1553

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Kettering-Meyer Laboratory, Southern Research Institute, P.O. Box 55 305, 35255-5305, Birmingham, AL, USA

    Lee J. Wilkoff, Elizabeth A. Dulmadge & Geetha Vasanthakumar

  2. Department of Microbiology and Immunology, Vanderbilt University, School of Medicine, 37232, Nashville, TN, USA

    John P. Donahue

Authors
  1. Lee J. Wilkoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth A. Dulmadge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Geetha Vasanthakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John P. Donahue
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was supported by Public Health Service grant CA-40421 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilkoff, L.J., Dulmadge, E.A., Vasanthakumar, G. et al. Etoposide-resistant human colon and lung adenocarcinoma cell lines exhibit sensitivity to homoharringtonine. Cancer Chemother. Pharmacol. 33, 149–153 (1993). https://doi.org/10.1007/BF00685333

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00685333

Keywords

Search

Navigation