A Novel Role for Raloxifene Nanomicelles in Management of Castrate Resistant Prostate CancerReport as inadecuate




A Novel Role for Raloxifene Nanomicelles in Management of Castrate Resistant Prostate Cancer - Download this document for free, or read online. Document in PDF available to download.

BioMed Research International - Volume 2014 2014, Article ID 323594, 14 pages -

Research Article

Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand

Department of Oncology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

Received 19 November 2013; Accepted 26 December 2013; Published 6 February 2014

Academic Editor: Giovanni Luca Gravina

Copyright © 2014 Sebastien Taurin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Of patients with castrate resistant prostate cancer CRPC, less than 25–33% survive more than five years. Recent studies have implicated estrogen, acting either alone or synergistically with androgens in the development of castrate resistant prostate cancer. Several in vitro and in vivo studies, as well as a limited number of clinical trials, have highlighted the potential of selective estrogen receptor modulators, such as raloxifene Ral for the treatment of castrate resistant prostate cancer. However, the poor oral bioavailability and metabolism of selective estrogen receptor modulators limit their efficiency in clinical application. To overcome these limitations, we have used styrene co-maleic acid SMA micelle to encapsulate raloxifene. Compared to free drug, SMA-Ral micelles had 132 and 140% higher cytotoxicity against PC3 and DU 145 prostate cell lines, respectively. SMA-Ral effectively inhibits cell cycle progression, increases apoptosis, and alters the integrity of tumor spheroid models. In addition, the micellar system induced changes in expression and localization of estrogen receptors, epidermal growth factor receptor EGFR, and downstream effectors associated with cell proliferation and survival. Finally, SMA-Ral treatment decreased migration and invasion of castrate resistant prostate cancer cell lines. In conclusion, SMA-Ral micelles can potentially benefit new strategies for clinical management of castrate resistant prostate cancer.





Author: Sebastien Taurin, Hayley Nehoff, Thalita van Aswegen, Rhonda J. Rosengren, and Khaled Greish

Source: https://www.hindawi.com/



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