Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis
Kyoungsook Park1, Kyusam Choi, Hyemee Kim
1Department of, Molecular Therapy Research Center, Sungkyunkwan University, Cancer Center B4-193, Samsung Medical Center, Seoul 135-710, Korea.
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.
Insights
Isoflavone-deprived soy peptide prevents mammary tumors in rats by inhibiting heat shock protein 90 (HSP90) and nuclear factor-kappa B (NF-κB) activation. This dietary intervention also promotes apoptosis and growth arrest, suggesting cancer chemoprevention potential.
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- Nuclear factor-kappa B (NF-κB) pathway deregulation drives cancer proliferation, angiogenesis, and metastasis.
- Heat shock protein 90 (HSP90) is crucial for NF-κB activation and stabilizes proteins regulating cell cycle and apoptosis.
- NF-κB suppression is a validated strategy for cancer chemoprevention.
Purpose of the Study:
- To investigate the chemopreventive effects of isoflavone-deprived soy peptide on 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced rat mammary tumorigenesis.
- To elucidate the underlying molecular mechanisms of soy peptide's action in cancer suppression.
Main Methods:
- Rats were administered a diet containing soy peptide (3.3 g/rat/day) or a control diet during DMBA exposure.
- Tumor incidence, multiplicity, and latency were assessed.
- Expression levels of HSP90, NF-κB pathway components, p21, p53, caspase-3, and vascular endothelial growth factor (VEGF) were analyzed.
- In vitro studies used human breast MCF-7 tumor cells treated with soy peptide.
Main Results:
- Dietary soy peptide significantly reduced mammary tumor incidence (50%) and multiplicity (49%) while extending tumor latency.
- Soy peptide administration markedly inhibited HSP90 expression, suppressing NF-κB activation.
- Treatment upregulated pro-apoptotic proteins (p21, p53, caspase-3) and downregulated VEGF.
- In vitro, soy peptide inhibited MCF-7 cell growth and induced apoptosis dose-dependently.
Conclusions:
- Isoflavone-deprived soy peptide exhibits significant chemopreventive and tumor-suppressive effects against mammary carcinogenesis in vivo.
- The mechanism involves inhibition of the HSP90/NF-κB pathway, induction of apoptosis, and cell cycle arrest.
- Soy peptide demonstrates potential as a dietary agent for cancer prevention and therapy.
More Related Videos
Related Concept Videos
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:23Abnormal Proliferation
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:31The Intrinsic Apoptotic Pathway
02:59Cancer Prevention
Some...