title: Amygdalin blocks the in vitro adhesion and invasion of renal cell carcinoma cells by an integrin-dependent mechanism.
abstract: Information about the natural compound amygdalin, which is employed as an antitumor agent, is sparse and thus its efficacy remains controversial. In this study, to determine whether amygdalin exerts antitumor effects on renal cell carcinoma (RCC) cells, its impact on RCC metastatic activity was investigated. The RCC cell lines, Caki-1, KTC-26 and A498, were exposed to amygdalin from apricot kernels, and adhesion to human vascular endothelium, immobilized collagen or fibronectin was investigated. The influence of amygdalin on chemotactic and invasive activity was also determined, as was the influence of amygdalin on surface and total cellular α and β integrin expression, which are involved in metastasis. We noted that amygdalin caused significant reductions in chemotactic activity, invasion and adhesion to endothelium, collagen and fibronectin. Using FACScan analysis, we noted that amygdalin also induced reductions, particularly in integrins α5 and α6, in all three cell lines. Functional blocking of α5 resulted in significantly diminished adhesion of KTC-26 and A498 to collagen and also in decreased chemotactic behavior in all three cell lines. Blocking α6 integrin significantly reduced chemotactic activity in all three cell lines. Thus, we suggest that exposing RCC cells to amygdalin inhibits metastatic spread and is associated with downregulation of α5 and α6 integrins. Therefore, we posit that amygdalin exerts antitumor activity in vitro, and this may be linked to integrin regulation.
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Juengel
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Masud
authors.initials: M
authors.lastname: Afschar
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Makarević
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Rutz
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Tsaur
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Mani
authors.affiliation: Department of Vascular and Endovascular Surgery, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Nelson
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haferkamp
authors.affiliation: Department of Urology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Blaheta
mesh_terms: D000678:Amygdalin / Q000494:pharmacology*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D039482:Integrin alpha5 / Q000378:metabolism; D039503:Integrin alpha6 / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism*
chemical_list: D039001:Integrin alpha Chains; D039482:Integrin alpha5; D039503:Integrin alpha6; D039641:Integrin beta Chains; D016023:Integrins; D000678:Amygdalin