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Research Paper
Human chorionic gonadotropin (hCG) interacts with lovastatin and ionizing radiation to modulate prostate cancer cell viability in vivo
Hossein Hamed, Clint Mitchell, Clint Mitchell, Margaret A. Park, David Hanna, Aditi Pandya Martin, Benjamin Harrison, William Hawkins, Paul B. Fisher, Steven Grant, Adly Yacoub, Michael P. Hagan and Paul Dent
volume 7 | issue 4
April 2008Pages: 587 - 593
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The ability of human chorionic gonadotropin (hCG) to modify prostate carcinoma viability in vitro and in vivo when combined with the HMG CoA reductase inhibitor lovastatin and ionizing radiation was investigated. Treatment of PC-3 cells in vitro with hCG caused a modest increase in numbers of non-viable cells within 96h. Treatment of cells with hCG followed by exposure to the HMG CoA reductase inhibitor lovastatin suppressed AKT phosphorylation and enhanced the cytotoxic effects of hCG. The cytotoxic effects of hCG were blocked by expression of BCL-XL and dominant negative caspase 9. Treatment of mice bearing PC-3 flank tumors with lovastatin and hCG significantly reduced tumor volume within 7 days; this was also reflected in decreased ex vivo colony survival of the cells which correlated with increased cleavage of pro-caspase 3 and reduced Ki67 immuno-reactivity. In vitro, treatment of PC-3 cells with hCG followed by exposure to ionizing radiation enhanced the cytotoxic effects of hCG, that was further enhanced by lovastatin. In vivo, hCG radiosensitized PC-3 tumors and significantly enhanced the lethality of hCG and lovastatin treatment. Collectively, our findings argue that treatment of PC-3 prostate cancer tumors with hCG, lovastatin and radiation represents a potential novel therapeutic approach.
Authors
Hossein Hamed
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
Clint Mitchell
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
Clint Mitchell
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
Margaret A. Park
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
David Hanna
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
Aditi Pandya Martin
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
Benjamin Harrison
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
William Hawkins
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
Paul B. Fisher
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
Steven Grant
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
Adly Yacoub
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
Michael P. Hagan
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.
Paul Dent
Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, 901 19th Street South, BMR2-502, Birmingham, AL 35294.