TY - JOUR
T1 - The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN
T2 - Similarities and distinct actions from soy isoflavone genistein
AU - Pabona, John Mark P.
AU - Dave, Bhuvanesh
AU - Su, Ying
AU - Montales, Maria Theresa E.
AU - De Lumen, Ben O.
AU - De Mejia, Elvira G.
AU - Rahal, Omar M.
AU - Simmen, Rosalia C.M.
N1 - Funding Information:
Acknowledgments This work was supported by the United States Department of Agriculture [CRIS 6251-5100002-06S, Arkansas Children’s Nutrition Center] and the Department of Defense Breast Cancer Research Program (W81XWH-08-1-0548) grants to R.C.M.S.
PY - 2013/1
Y1 - 2013/1
N2 - Breast cancer is the leading cause of cancer deaths in women. Diet and lifestyle are major contributing factors to increased breast cancer risk. While mechanisms underlying dietary protection of mammary tumor formation are increasingly elucidated, there remains a dearth of knowledge on the nature and precise actions of specific bioactive components present in foods with purported health effects. The 43-amino acid peptide lunasin (LUN) is found in soybeans, is bioavailable similar to the isoflavone genistein (GEN), and thus may mediate the beneficial effects of soy food consumption. Here, we evaluated whether LUN displays common and distinct actions from those of GEN in non-malignant (mouse HC11) and malignant (human MCF-7) mammary epithelial cells. In MCF-7 cells, LUN up-regulated tumor suppressor phosphatase and tensin homolog deleted in chromosome ten (PTEN) promoter activity, increased PTEN transcript and protein levels and enhanced nuclear PTEN localization, similar to that shown for GEN in mammary epithelial cells. LUN-induced cellular apoptosis, akin to GEN, was mediated by PTEN, but unlike that for GEN, was p53-independent. LUN promoted E-cadherin and β-catenin non-nuclear localization similar to GEN, but unlike GEN, did not influence the proliferative effects of oncogene Wnt1 on HC11 cells. Further, LUN did not recapitulate GEN inhibitory effects on expansion of the cancer stem-like/progenitor population in MCF-7 cells. Results suggest the concerted actions of GEN and LUN on cellular apoptosis for potential mammary tumor preventive effects and highlight whole food consumption rather than intake of specific dietary supplements with limited biological effects for greater health benefits.
AB - Breast cancer is the leading cause of cancer deaths in women. Diet and lifestyle are major contributing factors to increased breast cancer risk. While mechanisms underlying dietary protection of mammary tumor formation are increasingly elucidated, there remains a dearth of knowledge on the nature and precise actions of specific bioactive components present in foods with purported health effects. The 43-amino acid peptide lunasin (LUN) is found in soybeans, is bioavailable similar to the isoflavone genistein (GEN), and thus may mediate the beneficial effects of soy food consumption. Here, we evaluated whether LUN displays common and distinct actions from those of GEN in non-malignant (mouse HC11) and malignant (human MCF-7) mammary epithelial cells. In MCF-7 cells, LUN up-regulated tumor suppressor phosphatase and tensin homolog deleted in chromosome ten (PTEN) promoter activity, increased PTEN transcript and protein levels and enhanced nuclear PTEN localization, similar to that shown for GEN in mammary epithelial cells. LUN-induced cellular apoptosis, akin to GEN, was mediated by PTEN, but unlike that for GEN, was p53-independent. LUN promoted E-cadherin and β-catenin non-nuclear localization similar to GEN, but unlike GEN, did not influence the proliferative effects of oncogene Wnt1 on HC11 cells. Further, LUN did not recapitulate GEN inhibitory effects on expansion of the cancer stem-like/progenitor population in MCF-7 cells. Results suggest the concerted actions of GEN and LUN on cellular apoptosis for potential mammary tumor preventive effects and highlight whole food consumption rather than intake of specific dietary supplements with limited biological effects for greater health benefits.
KW - Apoptosis
KW - Breast cancer
KW - Genistein
KW - Lunasin
KW - Mammary epithelial
KW - PTEN
KW - Soy
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U2 - 10.1007/s12263-012-0307-5
DO - 10.1007/s12263-012-0307-5
M3 - Article
C2 - 22864686
AN - SCOPUS:84872402990
SN - 1555-8932
VL - 8
SP - 79
EP - 90
JO - Genes and Nutrition
JF - Genes and Nutrition
IS - 1
ER -