RGD Reference Report - Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis. - Rat Genome Database

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Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis.

Authors: Park, K  Choi, K  Kim, H  Kim, K  Lee, MH  Lee, JH  Kim Rim, JC 
Citation: Park K, etal., Exp Mol Med. 2009 Jun 30;41(6):371-81.
RGD ID: 5686847
Pubmed: PMID:19322027   (View Abstract at PubMed)
PMCID: PMC2705857   (View Article at PubMed Central)
DOI: DOI:10.3858/emm.2009.41.6.042   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Ductal Carcinoma  ISOHsp90aa1 (Rattus norvegicus)5686847; 5686847 RGD 
Ductal Carcinoma  IDA 5686847 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hsp90aa1  (heat shock protein 90 alpha family class A member 1)

Genes (Mus musculus)
Hsp90aa1  (heat shock protein 90, alpha (cytosolic), class A member 1)

Genes (Homo sapiens)
HSP90AA1  (heat shock protein 90 alpha family class A member 1)


Additional Information