title: Autophagy regulates lipolysis and cell survival through lipid droplet degradation in androgen-sensitive prostate cancer cells.
abstract: BACKGROUND
  Androgen deprivation therapy, one of the standard treatments for prostate cancer (PCa) induces apoptosis, as well as autophagy in androgen-responsive PCa cells. As autophagy can promote either cell survival or death, it is important to understand its role in PCa treatment. The objective of this study was to elucidate the function of autophagy in lipid droplet (LD) homeostasis and survival in androgen-sensitive PCa cells.
  
  
  METHODS
  To produce androgen deprivation, charcoal filtered serum or the androgen inhibitor casodex were used in LNCaP and LAPC4 cells. Autophagy was monitored by immunofluorescence/confocal microscopy and immunoblot analysis. Levels of intracellular LDs and triacyglycerols after the inhibition of autophagy by 3-methyladenine, bafilomycin A(1) , or si-ATG5 were quantified by three independent methods, Oil Red O staining, triacyglycerols lipase assay, and nuclear magnetic resonance.
  
  
  RESULTS
  Androgen deprivation induced autophagy and the depletion of LDs in both of the androgen-sensitive PCa cell lines examined, whereas the blockage of autophagy by pharmacological or genetic means inhibited LD degradation and therefore lipolysis and cell growth. In addition, under androgen deprivation, increased colocalization of LDs and autophagic vesicles was observed in LNCaP cells, which can be further enhanced by blocking the autophagic flux.
  
  
  CONCLUSIONS
  Autophagy mediates LD degradation and lipolysis in androgen-sensitive PCa cells during androgen deprivation which aids the survival of PCa cells during hormone therapy.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Ramesh R
authors.initials: RR
authors.lastname: Kaini
authors.forename: Laurel O
authors.initials: LO
authors.lastname: Sillerud
authors.forename: Siqin
authors.initials: S
authors.lastname: Zhaorigetu
authors.forename: Chien-An A
authors.initials: CA
authors.lastname: Hu
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009376:Neoplasms, Hormone-Dependent; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014105:Tosyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide