Prevention of mammary carcinogenesis in MMTV-neu mice by cruciferous vegetable constituent benzyl isothiocyanate.
Benzyl isothiocyanate (BITC), a constituent of edible cruciferous vegetables, inhibits growth of human breast cancer cells in culture. The present study provides in vivo evidence for efficacy of BITC for prevention of mammary cancer in MMTV-neu mice. Administration of BITC at 1 and 3 mmol/kg diet for 25 weeks markedly suppressed the incidence and/or burden of mammary hyperplasia and carcinoma in female MMTV-neu mice without causing weight loss or affecting neu protein level. For example, cumulative incidence of hyperplasia/carcinoma was significantly lower in mice fed BITC-supplemented diets compared with control mice (P = 0.01 by Fisher's test). The BITC-mediated prevention of mammary carcinogenesis correlated with suppression of cell proliferation and increased apoptosis. The average number of Ki-67-positive cells in the carcinoma lesions of 3 mmol BITC group was lower by approximately 21% (P < 0.05) compared with tumors from control mice. Apoptotic bodies in the mammary tumor were higher by about 2- to 2.5-fold in the 1 and 3 mmol BITC treatment groups (P < 0.05) compared with control group. The BITC administration also resulted in overexpression of E-cadherin and infiltration of CD3(+) T-cells in the tumor. Although BITC treatment increased cytotoxicity of natural killer (NK) cells in vitro, dietary feeding of BITC failed to augment NK cell lytic activity in an ex vivo assay. The present study demonstrating efficacy of BITC against mammary cancer in an animal model provides impetus to determine its activity in a clinical setting.
Warin
Renaud
R
Department of Pharmacology, and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Chambers
William H
WH
Potter
Douglas M
DM
Singh
Shivendra V
SV
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000096:biosynthesis; D048708:Cell Growth Processes / Q000187:drug effects; D002472:Cell Transformation, Viral; D004032:Diet; D005260:Female; D017879:Isothiocyanates / Q000008:administration & dosage* / Q000009:adverse effects; D007694:Killer Cells, Natural / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism / Q000517:prevention & control* / Q000821:virology; D008324:Mammary Tumor Virus, Mouse; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects
D016588:Anticarcinogenic Agents; D015820:Cadherins; D017879:Isothiocyanates; D018719:Erb-b2 Receptor Tyrosine Kinases; C031403:benzyl isothiocyanate; C524056:Erbb2 protein, mouse