title: Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro.
abstract: OBJECTIVE
  Despite impressive survival benefits from new agents to treat metastasized prostate cancer (PCa), progressive drug resistance hinders long-term response and restricts the efficacy of subsequent therapy. Due to reported antitumor activity of amygdalin and growing popularity for complementary and alternative medicine the potential of this natural, widely used substance to exert antineoplastic effects on prostate cancer cells has been assessed.
  
  
  METHODS
  LNCaP (castration-sensitive), DU-145 and PC3 cells (castration-resistant) were exposed to different concentrations of amygdalin for 24h or 2weeks. Cell growth was measured by the MTT test, clonal formation by the clonogenic assay. Flow cytometry served to investigate apoptosis and cell cycle phases. Cell cycle regulating proteins and the mTOR-akt signaling axis were analyzed by western blotting.
  
  
  RESULTS
  Amygdalin dose-dependently diminished tumor cell growth with maximum effects at 10mg/ml. Apoptosis of PC3 and LNCaP but not of DU-145 cells was reduced, whereas colony formation was suppressed in all cell lines. A decrease in the number of G2/M- and S-phase cells along with an elevated number of G0/G1-phase cells was recorded. The cell cycle proteins cdk 1, cdk 2 and cdk 4 as well as cyclin A, cyclin B and cyclin D3 were modulated by amygdalin after both 24h and 2weeks. Distinct effects on p19 and p27 expression and on Akt, Rictor and Raptor activation became evident only after 2weeks.
  
  
  CONCLUSIONS
  Amygdalin exhibits significant antitumor activity in both castration-sensitive and castration-resistant PCa cell lines and merits further evaluation for therapeutic purposes.
authors.affiliation: Department of Urology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Makarević
authors.affiliation: Department of Urology, Goethe-University, Frankfurt am Main, Germany. Electronic address: igor.tsaur@kgu.de.
authors.forename: Igor
authors.initials: I
authors.lastname: Tsaur
authors.affiliation: Department of Urology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Juengel
authors.affiliation: Department of Urology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Borgmann
authors.affiliation: Department of Vascular and Endovascular Surgery, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Nelson
authors.affiliation: Department of Urology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Department of Urology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Bartsch
authors.affiliation: Department of Urology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haferkamp
authors.affiliation: Department of Urology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Blaheta
mesh_terms: D000678:Amygdalin / Q000008:administration & dosage / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000678:Amygdalin
keywords: Amygdalin; Complementary and alternative medicine; Growth inhibition; Natural compounds; Prostate cancer