|Pabona, John -|
|Dave, Bhuvanesh -|
|Su, Ying -|
|Montales, Theresa -|
|Delumen, Ben -|
|Mejia, Elvira DE -|
|Rahal, Omar -|
|Simmen, Rosalia -|
Submitted to: Genes and Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 12, 2012
Publication Date: November 15, 2012
Citation: Pabona, J.M., Dave, B., Su, Y., Montales, T.M., Delumen, B.O., Mejia, E., Rahal, O., Simmen, R.C. 2012. The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein. Genes and Nutrition. 8(1):79-80. Interpretive Summary: Soy foods are composed of many different components with varying biological effects in mammary cells that might help in the prevention of breast cancer. The compound genistein is thought to be the most active of these components. In this study, we determined the effects of a protein called lunasin on mammary cells and found it to have some of the effects of genistein. However, not all of the biological effects of genistein were mimicked by lunasin. Thus, in order to obtain maximal health benefits, soy foods that contain all or most of the bioactive components are preferred to specific dietary supplements, such as lunasin.
Technical Abstract: 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 beta-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 foods consumption rather than intake of specific dietary supplements with limited biological effects for greater health benefits.