During carcinogenesis, NF-kappaB mediates processes associated with deregulation of the normal control of proliferation, angiogenesis, and metastasis. Thus, suppression of NF-kappaB has been linked with chemoprevention of cancer. Accumulating findings reveal that heat shock protein 90 (HSP90) is a molecular chaperone and a component of the IkappaB kinase (IKK) complex that plays a central role in NF-kappaB activation. HSP90 also stabilizes key proteins involved in cell cycle control and apoptosis signaling. We have determined whether the exogenous administration of isoflavone-deprived soy peptide prevents 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced rat mammary tumorigenesis and investigated the mechanism of action. Dietary administration of soy peptide (3.3 g/rat/day) significantly reduced the incidence of ductal carcinomas (50%), the number of tumors per multiple tumor-bearing rats (49%; P < 0.05), and extended the latency period of tumor development (8.07 +/- 0.92 weeks) compared to control diet animals (10.80 +/- 1.30; P < 0.05). Our results have further demonstrated that soy peptide (1) dramatically inhibits the expression of HSP90, thereby suppressing signaling pathway leading to NF-kappaB activation; (2) induces expression of p21, p53, and caspase-3 proteins; and (3) inhibits expression of VEGF. In agreement with our in vivo data, soy peptide treatment inhibited the growth of human breast MCF-7 tumor cells in a dose-dependent manner and induced apoptosis. Taken together, our in vivo and in vitro results suggest chemopreventive and tumor suppressive functions of isoflavone-deprived soy peptide by inducing growth arrest and apoptosis.
9,10-Dimethyl-1,2-benzanthracene ; Adenocarcinoma/*prevention & control ; Animals ; Apoptosis/*drug effects ; Breast Neoplasms/chemically induced/pathology/*prevention & control ; Cell Line, Tumor ; Chemoprevention ; Female ; Gene Expression Regulation, Neoplastic ; HSP90 Heat-Shock Proteins/genetics/metabolism ; Humans ; Isoflavones/chemistry ; NF-kappa B/genetics/metabolism ; Peptides/chemistry/isolation & purification/therapeutic use ; Rats ; Rats, Sprague-Dawley ; Soybean Proteins/chemistry/*isolation & purification/*therapeutic use ; Soybeans/chemistry

The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.
Adenocarcinoma/chemically induced/prevention & control ; Adult ; Animal ; Antineoplastic Agents, Phytogenic/*therapeutic use ; Cells, Cultured ; Cervix Neoplasms/chemically induced/prevention & control ; Clinical Trials ; Cytotoxicity Tests, Immunologic ; Disease Models, Animal ; Endometrial Neoplasms/pathology/prevention & control ; Endometrium/pathology ; Esophageal Neoplasms/pathology/prevention & control ; Esophagus/pathology ; Estradiol/blood ; Female ; Fibroadenoma/chemically induced/prevention & control ; Human ; Macrophages, Peritoneal/cytology/immunology ; Male ; Mammary Neoplasms, Experimental/chemically induced/prevention & control ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental/chemically induced/*prevention & control ; Nervous System Neoplasms/chemically induced/prevention & control ; Panax/*metabolism ; Precancerous Conditions/pathology/*prevention & control ; Rats ; Tissue Culture ; Uterine Neoplasms/chemically induced/prevention & control ; Vaginal Neoplasms/chemically induced/prevention & control