Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis.
10.3858/emm.2009.41.6.042
- Author:
Kyoungsook PARK
1
;
Kyusam CHOI
;
Hyemee KIM
;
Kwangbae KIM
;
Mi Hee LEE
;
Je Ho LEE
;
Jean Chinock KIM RIM
Author Information
1. Molecular Therapy Research Center, Sungkyunkwan University, Cancer Center B4-193, Samsung Medical Center, Seoul 135-710, Korea. eholee@gmail.com
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
breast neoplasms;
chemoprevention;
HSP90 heat-shock proteins;
isoflavones;
NF-kappaB;
soybean proteins
- MeSH:
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
- From:Experimental & Molecular Medicine
2009;41(6):371-380
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
