Cancer Chemotherapy and Pharmacology

, Volume 33, Issue 2, pp 149–153 | Cite as

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

  • Lee J. Wilkoff
  • Elizabeth A. Dulmadge
  • Geetha Vasanthakumar
  • John P. Donahue
Original Articles Etoposide Resistance, Homoharringtonine Sensitivity

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.

Keywords

Alkaloid Etoposide Vincristine Lung Adenocarcinoma Human Colon 

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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Lee J. Wilkoff
    • 1
  • Elizabeth A. Dulmadge
    • 1
  • Geetha Vasanthakumar
    • 1
  • John P. Donahue
    • 2
  1. 1.Kettering-Meyer LaboratorySouthern Research InstituteBirminghamUSA
  2. 2.Department of Microbiology and ImmunologyVanderbilt University, School of MedicineNashvilleUSA

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