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Abiraterone and Ionizing Radiation Alter the Sphingolipid Homeostasis in Prostate Cancer Cells

  • Valentina Murdica
  • Giulia Mancini
  • Nicoletta Loberto
  • Rosaria Bassi
  • Paola Giussani
  • Nadia Di Muzio
  • Chiara Deantoni
  • Alessandro Prinetti
  • Massimo Aureli
  • Sandro SonninoEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1112)

Abstract

Prostate cancer (PC) is one of the most common leading causes of cancer-related death in men. Currently, the main therapeutic approaches available for PC are based on the androgen deprivation and on radiotherapy. However, despite these treatments being initially effective in cancer remission, several patients undergo recurrence, developing a most aggressive and resistant PC.

Emerging evidence showed that abiraterone acetate drug will reduce PC recurrence by a mechanism independent of the inhibition of Cytochrome P450 17α-hydroxylase/17,20-lyase. Here we describe the involvement in the abiraterone-mediated PC cell death of a particular class of bioactive lipids called sphingolipids (SL). Sphingolipids are components of plasma membrane (PM) that organize macromolecular complexes involved in the control of several signaling pathways including the tumor cell death induced by radiotherapy. Here, we show for the first time that both in androgen-sensitive and insensitive PC cells abiraterone and ionizing radiation induce a reorganization of the plasma membrane SL composition. This event is triggered by activation of the PM-associated glycohydrolases that induce the production of cytotoxic ceramide by the in situ hydrolyses of glycosphingolipids. Taken together our data open a new scenario on the SL involvement in the therapy of PC.

Keywords

Ionizing radiation Abiraterone Sphingolipids Plasma membrane Prostate cancer Glycohydrolases Sialidase Neu3 

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Valentina Murdica
    • 1
  • Giulia Mancini
    • 1
  • Nicoletta Loberto
    • 1
  • Rosaria Bassi
    • 1
  • Paola Giussani
    • 1
  • Nadia Di Muzio
    • 2
  • Chiara Deantoni
    • 2
  • Alessandro Prinetti
    • 1
  • Massimo Aureli
    • 1
  • Sandro Sonnino
    • 1
    Email author
  1. 1.Department of Medical Biotechnology and Translational MedicineUniversity of MilanoMilanItaly
  2. 2.Department of RadiotherapyHospital San RaffaeleMilanItaly

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