title: Inhibition of Survivin Is Associated with Zoledronic Acid-induced Apoptosis of Prostate Cancer Cells.
abstract: OBJECTIVE
  Evidence suggests that zoledronic acid (ZA) exerts direct antitumor effects on cancer cells but the underlying mechanisms of these actions are unknown. This study investigated the possible involvement of survivin in the antiproliferative effects of ZA in prostate cancer.
  
  
  METHODS
  3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye reduction assay was used to assess cell viability and acridine orange/ethidium bromide double staining to analyze cell death. Human Apoptosis Array evaluated the expression of apoptosis-related proteins. Survivin protein was measured by western blot technique and miR-203 levels were quantified by quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  ZA induced inhibition of cell proliferation and apoptosis activation, with down-regulation of survivin protein. A negative regulation at gene expression level may be hypothesized because we observed a significant decrease of survivin mRNA level and an increase of miR-203 expression after ZA exposure.
  
  
  CONCLUSIONS
  This study provides evidence that ZA may directly inhibit cancer cell proliferation, identifying survivin as one of its downstream targets.
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine martina.fragni@unibs.it.
authors.forename: Martina
authors.initials: M
authors.lastname: Fragni
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine.
authors.forename: Sara Anna
authors.initials: SA
authors.lastname: Bonini
authors.affiliation: Unit of Urology, Scientific Institute and University San Raffaele Hospital, Milan, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Stabile
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine.
authors.forename: Serena
authors.initials: S
authors.lastname: Bodei
authors.affiliation: Urology Unit University of Brescia, Brescia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cristinelli
authors.affiliation: Urology Unit University of Brescia, Brescia, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Simeone
authors.affiliation: Urology Unit University of Brescia, Brescia, Italy Division of Urology, City of Brescia Clinical Institute, Brescia, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Zani
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine.
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Spano
authors.affiliation: Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Memo
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sigala
mesh_terms: D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin; D000077211:Zoledronic Acid
chemical_list: C107489:BIRC5 protein, human; D004164:Diphosphonates; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D000077022:Survivin; D000077211:Zoledronic Acid
keywords: Prostate cancer; apoptosis; miR-203; survivin; zoledronic acid