Suppression of 7,12‐dimethylbenz(a)anthracene‐induced mammary tumorigenesis by glyceollins

SCOPE: Our previous study showed that glyceollins induced phase 2 detoxifying and antioxidant enzymes. As chemical carcinogens can be detoxified by metabolic activity of phase 2 enzymes, subsequently decreasing their tumorigenic potential, we investigated whether 7,12‐dimethylbenz(a)anthracene (DMBA...

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Published in:Molecular nutrition & food research 2015-05, Vol.59 (5), p.907-917
Main Authors: Kim, Bo Ram, Seo, Ji‐Yeon, Sung, Mi‐Kyung, Park, Jung Han Yoon, Suh, Hwa‐Jin, Liu, Kwang Hyeon, Kim, Jong‐Sang
Format: Article
Language:English
Subjects:
9,10-Dimethyl-1,2-benzanthracene
animal models
Animals
anthracenes
antioxidants
body weight
carcinogenesis
carcinogens
Cytochrome P-450 CYP1A1 - metabolism
Deoxyguanosine - analogs & derivatives
Deoxyguanosine - blood
DMBA
enzymes
estrogenic properties
Female
Glyceollins
mammary neoplasms (animal)
Mammary Neoplasms, Experimental - chemically induced
Mammary Neoplasms, Experimental - prevention & control
Mammary tumor
Mice
Mice, Inbred C57BL
Mucin-1 - analysis
NF-E2-Related Factor 2 - metabolism
Nrf2
Phase 2 detoxifying enzymes
protective effect
Pterocarpans - pharmacology
signal transduction
survival rate
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Summary:SCOPE: Our previous study showed that glyceollins induced phase 2 detoxifying and antioxidant enzymes. As chemical carcinogens can be detoxified by metabolic activity of phase 2 enzymes, subsequently decreasing their tumorigenic potential, we investigated whether 7,12‐dimethylbenz(a)anthracene (DMBA)‐induced mammary tumorigenesis could be attenuated by treatment with glyceollins in a mouse model. METHODS AND RESULTS: Pretreatment with glyceollins (5 mg/kg body weight) caused a significant reduction in tumor formation and an increase in survival rate. The protective effect of glyceollins against DMBA‐induced tumorigenesis was found to be mainly associated with their potential to induce phase 2/antioxidant enzymes that are, in turn, regulated by the nuclear factor E2‐related factor 2 signaling pathway, and to a less extent to suppress phase 1 enzymes. As glyceollins increased the number of terminal end buds, a tumor‐prone mammary tissue type in mice, it is unlikely that they exert their antitumorigenic action through their estrogenic activity. CONCLUSION: Glyceollins were found to have a protective effect in a chemically induced mammary tumor model.
ISSN:1613-4125
1613-4133
DOI:10.1002/mnfr.201400726