Soy-derived isoflavones inhibit the growth of canine lymphoid cell lines.
OBJECTIVE
This study aimed to evaluate the in vitro effects of genistein, both pure genistein and a commercially available form of genistein called Genistein Combined Polysacharride (GCP), against two canine B-cell lymphoid cell lines and determine the oral bioavailability of GCP when fed to normal dogs.


METHODS
The in vitro effect of genistein and GCP was evaluated using cell proliferation and apoptotic assays. The IC50 of both compounds was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay and propidium idodide staining. Apoptosis was evaluated using Annexin V staining, caspase 3 and 9 staining, and DNA laddering. Cell cycle analysis and Bcl-2/Bax ratios were also examined. An initial dose escalating pharmacokinetic study was used to determine if therapeutic serum levels of genistein could be reached with oral dosing of GCP in normal dogs.


RESULTS
The 72-hour in vitro IC50 of genistein and GCP against the GL-1 and 17-71 cells were both 10 microg/mL and 20 microg/mL, respectively. GCP led to cell death in both cell lines via apoptosis and treated cells exhibited increased Bax:Bcl-2 ratios. The serum concentrations of genistein in normal dogs given increasing oral doses of GCP did not reach the 72-hour in vitro IC50 in a dose escalation study.


CONCLUSIONS
The results of these studies support the notion that canine high-grade B-cell lymphoma may represent a relevant large animal model of human non-Hodgkin's lymphoma to investigate the utility of GCP in chemopreventive and/or treatment strategies that may serve as a prelude to human clinical lymphoma trials.
Jamadar-Shroff
Vahbiz
V
Department of Clinical Sciences, North Carolina State College of Veterinary Medicine, Raleigh, North Carolina 27606, USA.
Papich
Mark G
MG
Suter
Steven E
SE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000502:physiology; D053453:Caspase 9 / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D019833:Genistein / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D008297:Male; D011134:Polysaccharides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000032:analysis
D011134:Polysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C473311:genistein combined polysaccharide; D019833:Genistein; D053148:Caspase 3; D053453:Caspase 9