Bicalutamide failure in prostate cancer treatment: Involvement of Multi Drug Resistance proteins

Nicola Antonio Colabufo, Vincenzo Pagliarulo, Francesco Berardi, Marialessandra Contino, Carmela Inglese, Mauro Niso, Patrizia Ancona, Giancarlo Albo, Arcangelo Pagliarulo, Roberto Perrone

Research output: Contribution to journalArticle

Abstract

Prolonged bicalutamide treatment induced pathology regression although relapses with a more aggressive form of prostate cancer have been observed. This failure could be due to androgen receptor mutation. In the present work we hypothesized an alternative mechanism responsible for bicalutamide failure involving activity of ATP-binding cassette (ABC) pumps such as P-glycoprotein, Breast Cancer Receptor Protein (BCRP), and Multi Resistant Proteins (MRPs) that extrude the androgen antagonist from the cell membrane. As experimental models androgen-dependent (LnCap) and androgen-independent (PC-3) prostate cancer cell lines have been employed. Bicalutamide has been tested in the cell lines mentioned above in the absence and in the presence of MC18, our potent P-glycoprotein/BCRP/MRP1 inhibitor. The results displayed that bicalutamide antiproliferative effect at 72 h was ameliorated in LnCap cells (EC50 from 51.9 ± 6.1 μM to 17.8 ± 2.6 μM in the absence and in the presence of MC18, respectively) and restored in PC-3 cells (EC50 from 150 ± 2.4 μM to 60 ± 3.5 μM in the absence and in the presence of MC18, respectively). Moreover, we established the contribution of each transporter employing stable transfected cells (MDCK) overexpressing P-glycoprotein or BCRP or MRP1 pump. The results displayed that P-glycoprotein and BCRP were involved in bicalutamide efflux while MRP1 was unable to bind the antiandrogen drug.

Original languageEnglish
Pages (from-to)38-42
Number of pages5
JournalEuropean Journal of Pharmacology
Volume601
Issue number1-3
DOIs
Publication statusPublished - Dec 28 2008

Keywords

  • BCRP
  • Bicalutamide
  • Calcein-AM
  • MRP1
  • P-glycoprotein

ASJC Scopus subject areas

  • Pharmacology

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    Colabufo, N. A., Pagliarulo, V., Berardi, F., Contino, M., Inglese, C., Niso, M., Ancona, P., Albo, G., Pagliarulo, A., & Perrone, R. (2008). Bicalutamide failure in prostate cancer treatment: Involvement of Multi Drug Resistance proteins. European Journal of Pharmacology, 601(1-3), 38-42. https://doi.org/10.1016/j.ejphar.2008.10.038