Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2

PLoS One. 2014 Aug 19;9(8):e105590. doi: 10.1371/journal.pone.0105590. eCollection 2014.

Abstract

Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdalin / pharmacology*
  • Antineoplastic Agents / pharmacology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclin A / metabolism*
  • Cyclin-Dependent Kinase 2 / metabolism*
  • G1 Phase / drug effects
  • Humans
  • Proto-Oncogene Proteins c-akt / metabolism
  • Resting Phase, Cell Cycle / drug effects
  • TOR Serine-Threonine Kinases / metabolism
  • Urinary Bladder Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • Cyclin A
  • Amygdalin
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2

Grant support

This work was supported by the “Brigitta und Norbert Muth Stiftung” (http://www.muth-stiftung.de) and the “Freunde und Förderer der Goethe-Universität Frankfurt” (http://www2.uni-frankfurt.de). The funding was received by RAB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.