Carcinogenesis Advance Access published online on June 15, 2006
Carcinogenesis, doi:10.1093/carcin/bgl109
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Cancer Chemoprevention and Support Program, Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210
* To whom correspondence should be addressed. Angiogenesis, the formation of new blood vessels, is critical to tumor growth and metastasis. Vascular endothelial growth factor (VEGF), an important angiogenic activator, is essential for angiogenesis. Our laboratory has used a rodent model of human esophageal squamous cell carcinoma (ESCC) to identify putative chemopreventive agents for this disease and determine their mechanisms of action. We reported that dietary black raspberry powder (BRB) inhibits N-nitrosomethylbenzylamine (NMBA)-induced tumor development in the rat esophagus by inhibiting the formation of DNA adducts and reducing the proliferation rate of preneoplastic cells. On a molecular level, BRB down-regulates the expression of c-Jun, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). In this study we analyzed the effect of BRB on angiogenesis. VEGF expression was determined by real-time reverse-transcription polymerase chain reaction and immunohistochemical analysis of microvessel density (MVD). BRB significantly suppressed VEGF-C expression from a 2.38 (± 0.34)-fold increase in animals treated with NMBA alone to a 1.08 (± 0.22)-fold increase in animals treated with NMBA plus BRB (P < 0.005). The MVD of esophagus was decreased from 53.7 ± 5.6 vessels/cm in animals treated with NMBA alone to 22.6 ± 2.6 vessels/cm in animals treated with NMBA plus BRB (P < 0.0001). Our data also suggest that down-regulation of VEGF is correlated with suppression of COX-2 (r2 = 0.86, P < 0.001) and iNOS (r2 = 0.81, P < 0.005). Because high vascularity is a risk factor for metastasis and tumor recurrence, BRB may have cancer therapeutic effects in human esophageal cancer.
Received January 17, 2006
Revised May 27, 2006
Accepted June 5, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Black raspberries inhibit N-nitrosomethylbenzylamine (NMBA)-induced angiogenesis in rat esophagus parallel to the suppression of COX-2 and iNOS
Tong Chen 1,
Miranda E. Rose 1,
Hyejeong Hwang 1,
Ronald G. Nines 1,
and
Gary D. Stoner 1 *
Gary D. Stoner, E-mail: gary.stoner{at}osumc.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. D. Stoner, L.-S. Wang, and B. C. Casto Laboratory and clinical studies of cancer chemoprevention by antioxidants in berries Carcinogenesis, September 1, 2008; 29(9): 1665 - 1674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Stoner, A. A. Dombkowski, R. K. Reen, D. Cukovic, S. Salagrama, L.-S. Wang, and J. F. Lechner Carcinogen-Altered Genes in Rat Esophagus Positively Modulated to Normal Levels of Expression by Both Black Raspberries and Phenylethyl Isothiocyanate Cancer Res., August 1, 2008; 68(15): 6460 - 6467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Mallery, J. C. Zwick, P. Pei, M. Tong, P. E. Larsen, B. S. Shumway, B. Lu, H. W. Fields, R. J. Mumper, and G. D. Stoner Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions Cancer Res., June 15, 2008; 68(12): 4945 - 4957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Shumway, L. A. Kresty, P. E. Larsen, J. C. Zwick, B. Lu, H. W. Fields, R. J. Mumper, G. D. Stoner, and S. R. Mallery Effects of a Topically Applied Bioadhesive Berry Gel on Loss of Heterozygosity Indices in Premalignant Oral Lesions Clin. Cancer Res., April 15, 2008; 14(8): 2421 - 2430. [Abstract] [Full Text] [PDF]
|
|