INTRODUCTION: The critical need for novel therapeutic approaches to pancreatic cancer treatment is clear. Genistein, a naturally occurring isoflavonoid, is active against certain solid malignancies, but its effect on pancreatic cancer is unknown. AIMS: To investigate the bioactivity of genistein in experimental pancreatic cancer in vitro and in vivo. METHODOLOGY: The effect of intraperitoneal genistein administration on local tumor growth and metastatic disease was determined in an orthotopic nude mouse model. Apoptosis in tumor specimens was determined by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) technique. In vitro, the effect of genistein on cell growth was assessed by cell count and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) colorimetric assay. Apoptosis was determined in vitro by DNA laddering and annexin-V. Caspase-3 and nuclear factor-kappaB activity were measured following genistein treatment. RESULTS: In vivo, genistein significantly improved survival, almost completely inhibited metastasis, and increased apoptosis in an orthotopic model of pancreatic cancer. In vitro genistein treatment resulted in apoptosis in all pancreatic cancer cell lines tested, and this appeared to be mediated by activation of caspase-3. CONCLUSION: These findings suggest that the antimetastatic effect of genistein treatment in vivo is mediated by induction of apoptosis. Genistein may have a therapeutic benefit for patients with pancreatic cancer, in particular after surgery, to prevent recurrence of metastatic disease.
INTRODUCTION: The critical need for novel therapeutic approaches to pancreatic cancer treatment is clear. Genistein, a naturally occurring isoflavonoid, is active against certain solid malignancies, but its effect on pancreatic cancer is unknown. AIMS: To investigate the bioactivity of genistein in experimental pancreatic cancer in vitro and in vivo. METHODOLOGY: The effect of intraperitoneal genistein administration on local tumor growth and metastatic disease was determined in an orthotopic nude mouse model. Apoptosis in tumor specimens was determined by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) technique. In vitro, the effect of genistein on cell growth was assessed by cell count and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) colorimetric assay. Apoptosis was determined in vitro by DNA laddering and annexin-V. Caspase-3 and nuclear factor-kappaB activity were measured following genistein treatment. RESULTS: In vivo, genistein significantly improved survival, almost completely inhibited metastasis, and increased apoptosis in an orthotopic model of pancreatic cancer. In vitro genistein treatment resulted in apoptosis in all pancreatic cancer cell lines tested, and this appeared to be mediated by activation of caspase-3. CONCLUSION: These findings suggest that the antimetastatic effect of genistein treatment in vivo is mediated by induction of apoptosis. Genistein may have a therapeutic benefit for patients with pancreatic cancer, in particular after surgery, to prevent recurrence of metastatic disease.
Authors: Peter Büchler; Amiq Gazdhar; Mario Schubert; Nathalia Giese; Howard A Reber; Oscar J Hines; Thomas Giese; Güralp O Ceyhan; Michael Müller; Markus W Büchler; Helmut Friess Journal: Ann Surg Date: 2005-12 Impact factor: 12.969
Authors: Peter Büchler; Howard A Reber; James S Tomlinson; Oliver Hankinson; Georgis Kallifatidis; Helmut Friess; Ingrid Herr; Oscar J Hines Journal: Neoplasia Date: 2009-02 Impact factor: 5.715
Authors: Hung Pham; Monica Chen; Hiroki Takahashi; Jonathan King; Howard A Reber; Oscar Joe Hines; Stephen Pandol; Guido Eibl Journal: Pancreas Date: 2012-11 Impact factor: 3.327