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Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro.

Abstract

AIMS

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.

MAIN 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.

KEY FINDINGS

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.

SIGNIFICANCE

Amygdalin exhibits significant antitumor activity in both castration-sensitive and castration-resistant PCa cell lines and merits further evaluation for therapeutic purposes.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Urology, Goethe-University, Frankfurt am Main, Germany.

    ,

    Department of Urology, Goethe-University, Frankfurt am Main, Germany. Electronic address: igor.tsaur@kgu.de.

    ,

    Department of Urology, Goethe-University, Frankfurt am Main, Germany.

    ,

    Department of Urology, Goethe-University, Frankfurt am Main, Germany.

    ,

    Department of Vascular and Endovascular Surgery, Goethe-University, Frankfurt am Main, Germany.

    ,

    Department of Urology, Goethe-University, Frankfurt am Main, Germany.

    ,

    Department of Urology, Goethe-University, Frankfurt am Main, Germany.

    ,

    Department of Urology, Goethe-University, Frankfurt am Main, Germany.

    Department of Urology, Goethe-University, Frankfurt am Main, Germany.

    Source

    Life sciences 147: 2016 Feb 15 pg 137-42

    MeSH

    Amygdalin
    Antineoplastic Agents, Phytogenic
    Apoptosis
    Blotting, Western
    Cell Cycle
    Cell Line, Tumor
    Dose-Response Relationship, Drug
    Flow Cytometry
    Humans
    Male
    Prostatic Neoplasms
    Prostatic Neoplasms, Castration-Resistant
    Time Factors

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    26827990

    Citation

    TY - JOUR T1 - Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro. AU - Makarević,Jasmina, AU - Tsaur,Igor, AU - Juengel,Eva, AU - Borgmann,Hendrik, AU - Nelson,Karen, AU - Thomas,Christian, AU - Bartsch,Georg, AU - Haferkamp,Axel, AU - Blaheta,Roman A, Y1 - 2016/01/29/ PY - 2015/8/10/received PY - 2016/1/22/revised PY - 2016/1/26/accepted PY - 2016/1/29/aheadofprint PY - 2016/2/2/entrez PY - 2016/2/2/pubmed PY - 2016/7/7/medline KW - Amygdalin KW - Complementary and alternative medicine KW - Growth inhibition KW - Natural compounds KW - Prostate cancer SP - 137 EP - 42 JF - Life sciences JO - Life Sci. VL - 147 N2 - AIMS: 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. MAIN 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. KEY FINDINGS: 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. SIGNIFICANCE: Amygdalin exhibits significant antitumor activity in both castration-sensitive and castration-resistant PCa cell lines and merits further evaluation for therapeutic purposes. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/26827990/Amygdalin_delays_cell_cycle_progression_and_blocks_growth_of_prostate_cancer_cells_in_vitro L2 - http://linkinghub.elsevier.com/retrieve/pii/S0024-3205(16)30039-X ER -