Prolonged exposure to (R)-bicalutamide generates a LNCaP subclone with alteration of mitochondrial genome

Sara Pignatta, Chiara Arienti, Wainer Zoli, Marzia Di Donato, Gabriella Castoria, Elisa Gabucci, Valentina Casadio, Mirella Falconi, Ugo De Giorgi, Rosella Silvestrini, Anna Tesei

Research output: Contribution to journalArticlepeer-review

Abstract

Advanced prostate cancers, initially sensitive to androgen deprivation therapy, frequently progress to the castration-resistant prostate cancer phenotype (CRPC) through mechanisms not yet fully understood. In this study we investigated mitochondrial involvement in the establishment of refractoriness to hormone therapy. Two human prostate cancer cell lines were used, the parental LNCaP and the resistant LNCaP-Rbic, the latter generated after continuous exposure to 20. μM of (R)-bicalutamide, the active enantiomer of Casodex®. We observed a significant decrease in mtDNA content and a lower expression of 8 mitochondria-encoded gene transcripts involved in respiratory chain complexes in both cell lines. We also found that (R)-bicalutamide differentially modulated dynamin-related protein (Drp-1) expression in LNCaP and LNCaP-Rbic cells. These data seem to indicate that the androgen-independent phenotype in our experimental model was due, at least in part, to alterations in mitochondrial dynamics and to a breakdown in the Drp-1-mediated mitochondrial network.

Original languageEnglish
Pages (from-to)314-324
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume382
Issue number1
DOIs
Publication statusPublished - Jan 25 2014

Keywords

  • (R)-bicalutamide
  • Hormone-resistance
  • Mitochondrial fission
  • MtDNA
  • Prostate cancer

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

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