title: Amygdalin inhibits the growth of renal cell carcinoma cells in vitro.
abstract: Although amygdalin is used by many cancer patients as an antitumor agent, there is a lack of information on the efficacy and toxicity of this natural compound. In the present study, the inhibitory effect of amygdalin on the growth of renal cell carcinoma (RCC) cells was examined. Amygdalin (10 mg/ml) was applied to the RCC cell lines, Caki-1, KTC-26 and A498, for 24 h or 2 weeks. Untreated cells served as controls. Tumor cell growth and proliferation were determined using MTT and BrdU tests, and cell cycle phases were evaluated. Expression of the cell cycle activating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1 and D3 as well as of the cell cycle inhibiting proteins p19 and p27 was examined by western blot analysis. Surface expression of the differentiation markers E- and N-cadherin was also investigated. Functional blockade by siRNA was used to determine the impact of several proteins on tumor cell growth. Amygdalin treatment caused a significant reduction in RCC cell growth and proliferation. This effect was correlated with a reduced percentage of G2/M-phase RCC cells and an increased percentage of cells in the G0/1-phase (Caki-1 and A498) or cell cycle arrest in the S-phase (KTC-26). Furthermore, amygdalin induced a marked decrease in cell cycle activating proteins, in particular cdk1 and cyclin B. Functional blocking of cdk1 and cyclin B resulted in significantly diminished tumor cell growth in all three RCC cell lines. Aside from its inhibitory effects on growth, amygdalin also modulated the differentiation markers, E- and N-cadherin. Hence, exposing RCC cells to amygdalin inhibited cell cycle progression and tumor cell growth by impairing cdk1 and cyclin B expression. Moreover, we noted that amygdalin affected differentiation markers. Thus, we suggest that amygdalin exerted RCC antitumor effects in vitro.
authors.affiliation: Department of Urology, Goethe-University Hospital, D-60590 Frankfurt am Main, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Juengel
authors.affiliation: Department of Urology, Goethe-University Hospital, D-60590 Frankfurt am Main, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Department of Urology, Goethe-University Hospital, D-60590 Frankfurt am Main, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Rutz
authors.affiliation: Department of Urology, Goethe-University Hospital, D-60590 Frankfurt am Main, Germany.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Makarevic
authors.affiliation: Department of Urology, Goethe-University Hospital, D-60590 Frankfurt am Main, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Tsaur
authors.affiliation: Department of Vascular and Endovascular Surgery, Goethe-University Hospital, D-60590 Frankfurt am Main, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Nelson
authors.affiliation: Department of Urology, Goethe-University Hospital, D-60590 Frankfurt am Main, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haferkamp
authors.affiliation: Department of Urology, Goethe-University Hospital, D-60590 Frankfurt am Main, Germany.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Blaheta
mesh_terms: D000678:Amygdalin / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019926:Cyclin B / Q000096:biosynthesis* / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans
chemical_list: D018797:Cell Cycle Proteins; D019926:Cyclin B; D000678:Amygdalin; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases