title: Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis.
abstract: During carcinogenesis, NF-gammaB mediates processes associated with deregulation of the normal control of proliferation, angiogenesis, and metastasis. Thus, suppression of NF-gammaB 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 IgammaB kinase (IKK) complex that plays a central role in NF-gammaB 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-gammaB 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.
authors.affiliation: Department of, Molecular Therapy Research Center, Sungkyunkwan University, Cancer Center B4-193, Samsung Medical Center, Seoul 135-710, Korea.
authors.forename: Kyoungsook
authors.initials: K
authors.lastname: Park
authors.forename: Kyusam
authors.initials: K
authors.lastname: Choi
authors.forename: Hyemee
authors.initials: H
authors.lastname: Kim
authors.forename: Kwangbae
authors.initials: K
authors.lastname: Kim
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Lee
authors.forename: Je Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Jean Chinock
authors.initials: JC
authors.lastname: Kim Rim