Activity of different anthracycline formulations in hormone-refractory prostate cancer cell lines: Role of golgi apparatus

Francesco Fabbri, Wainer Zoli, Silvia Carloni, Paola Ulivi, Chiara Arienti, Giovanni Brigliadori, Marco Montanari, Anna Tesei, Rosella Silvestrini, Dino Amadori

Research output: Contribution to journalArticlepeer-review

Abstract

The efficacy of therapy for hormone-refractory prostate cancer (HRPC) is still unsatisfactory and new agents and therapeutic modalities are needed. The aims of the present work were to examine the in vitro activity and mechanisms of action of doxorubicin (DX), pegylated liposomal DX (PLDX), and non-pegylated liposomal DX (NPLDX) in DU145 and taxane-resistant DU145-R HRPC cell lines. Drug activity and incorporation, apoptosis, and expression of cell death-related markers were evaluated by SRB test, cytofluorimetric assays, and Western blot, respectively. Among the different DX formulations, NPLDX showed the highest cytotoxic activity in both cell lines, with more than 50% of apoptotic cells at only 1/10 of the plasma peak concentration after 72h exposure. Anthracyclines, in particular NPLDX, were highly concentrated in the Golgi apparatus. Moreover, a significant increase was observed in the expression of CD95 receptor, GD3 ganglioside and, caspase-2 and -8 active forms in both cell lines followed by caspase-3 activation and mitochondrial membrane depolarization. The Golgi apparatus, probably acting as a stress sensor, intensified the conventional apoptotic mechanism induced by anthracyclines. Our data support the hypothesis that organelle-dependent initiation of cell death other than that induced by mitochondria and nucleus is a research area worthy of pursuing and suggest that the Golgi apparatus could be an ideal target for anti-cancer therapy. Of note, the activity of NLPDX in taxane-resistant DU145-R cells warrants further evaluation as second-line treatment of advanced HRPC after taxane failure.

Original languageEnglish
Pages (from-to)3035-3042
Number of pages8
JournalJournal of Cellular Physiology
Volume226
Issue number11
DOIs
Publication statusPublished - Nov 2011

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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