Voacamine, a bisindolic alkaloid from Peschiera fuchsiaefolia, enhances the cytotoxic effect of doxorubicin on multidrug-resistant tumor cells

  • Authors:
    • S. Meschini
    • M. Marra
    • A. Calcabrini
    • E. Federici
    • C. Galeffi
    • G. Arancia
  • View Affiliations

  • Published online on: December 1, 2003     https://doi.org/10.3892/ijo.23.6.1505
  • Pages: 1505-1513
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Multidrug-resistance (MDR) is largely caused by the efflux of therapeutics from the tumor cell by means of P-glycoprotein (P-gp), resulting in reduced efficacy of the chemotherapy. In order to overcome MDR, substances, such as verapamil and cyclosporin A (CsA), were employed. As these P-gp modulating agents did not seem promising in clinical practice, new compounds with a low degree of undesirable side effects, were introduced. In this study, bisindolic alkaloid voacamine was examined for its possible capability of enhancing the cytotoxic effect of doxorubicin (DOX) on drug resistant cells. Two different pairs of tumor cell lines were analyzed: the parental lymphoblastoid cell line CEM-WT and its MDR derivative CEM-R, the parental osteosarcoma cell line U-2 OS-WT and its resistant counterpart U-2 OS-R. These cell lines were characterized for their morphological features by scanning electron microscopy (SEM) and for the expression of the main drug transporters by flow cytometric analysis. The effects of voacamine on the cell survival and on both accumulation and efflux of DOX were then investigated. The intracellular distribution of DOX, given alone or in association with CsA or voacamine, was observed by laser scanning confocal microscopy. A differential effect of voacamine between sensitive and resistant cells on the intracellular DOX concentration and distribution was shown. In particular, voacamine induced a significant increase of drug retention and intranuclear location in resistant cells. The results of cell survival experiments revealed an enhancement of the cytotoxic effect of DOX induced by voacamine, confirmed by evident morphological changes observed by SEM. These findings suggest promising applications of this natural substance against MDR tumors.

Related Articles

Journal Cover

December 2003
Volume 23 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Meschini S, Marra M, Calcabrini A, Federici E, Galeffi C and Arancia G: Voacamine, a bisindolic alkaloid from Peschiera fuchsiaefolia, enhances the cytotoxic effect of doxorubicin on multidrug-resistant tumor cells. Int J Oncol 23: 1505-1513, 2003.
APA
Meschini, S., Marra, M., Calcabrini, A., Federici, E., Galeffi, C., & Arancia, G. (2003). Voacamine, a bisindolic alkaloid from Peschiera fuchsiaefolia, enhances the cytotoxic effect of doxorubicin on multidrug-resistant tumor cells. International Journal of Oncology, 23, 1505-1513. https://doi.org/10.3892/ijo.23.6.1505
MLA
Meschini, S., Marra, M., Calcabrini, A., Federici, E., Galeffi, C., Arancia, G."Voacamine, a bisindolic alkaloid from Peschiera fuchsiaefolia, enhances the cytotoxic effect of doxorubicin on multidrug-resistant tumor cells". International Journal of Oncology 23.6 (2003): 1505-1513.
Chicago
Meschini, S., Marra, M., Calcabrini, A., Federici, E., Galeffi, C., Arancia, G."Voacamine, a bisindolic alkaloid from Peschiera fuchsiaefolia, enhances the cytotoxic effect of doxorubicin on multidrug-resistant tumor cells". International Journal of Oncology 23, no. 6 (2003): 1505-1513. https://doi.org/10.3892/ijo.23.6.1505