|Pabona, John Mark -|
|Dave, Bhuvanesh -|
|Rahal, Omar -|
|Lumen, Ben -|
|Mejia, Elvira -|
|Simmen, Rosalia -|
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: December 15, 2010
Publication Date: April 1, 2011
Citation: Pabona, J.P., Dave, B., Rahal, O., Lumen, B.O., Mejia, E., Simmen, R.C. 2011. Soy peptide lunasin induces pten-mediated apoptosis in human breast cancer cells. The FASEB Journal. 25(Meeting Abstract):213.3. Interpretive Summary: Breast cancer is the most frequently diagnosed life-threatening cancer and currently the leading cause of cancer death among women. Several studies have shown that diet modifies the risk of developing breast cancer. One of these is soy protein, which has been implicated to have protective effects against breast cancer. One of the most studied soy component is genistein (GEN) and the identity of other components remains relatively unknown. In this study, we further characterize other bioactive component of soy which is lunasin (LUN) that was detected in sera of rats and humans consuming soy-rich diets. Our findings suggest that this bioactive component mediate cell death in human breast cancer cells.
Technical Abstract: The tumor suppressor PTEN inhibits the AKT signaling pathway whose unrestrained activity underlies many human malignancies. Previously we showed that dietary intake of soy protein isolate (SPI) enhanced PTEN expression in mammary tissue of rats with lower NMU-induced mammary tumor incidence relative to those fed casein-based diet. While epidemiological studies corroborate the breast cancer protective effects of soy, specifically of the major soy isoflavone genistein (GEN), the identity of other bioactive soy components remains relatively unknown. Here we evaluated the effects of lunasin, a soybean peptide previously detected in sera of rats and humans consuming soy-rich diets, on PTEN-mediated apoptosis of the mammary carcinoma cell line MCF-7. Lunasin (2 µM >50 nM) increased PTEN expression and nuclear localization (by 2.5-fold); enhanced PTEN-mediated cellular apoptosis (by 10-15-fold); and altered levels of p53 (increased) and p21WAF1 (decreased) transcripts (P<0.05). GEN (2 µM >20 nM) elicited similar effects as lunasin on PTEN expression and PTEN-mediated apoptosis in MCF-7 cells. Lunasin and GEN are known to regulate core histone acetylation by which PTEN promoter activity is similarly controlled. Findings suggest that activation of PTEN expression by bioactive soy components, possibly via epigenetic mechanisms may underlie breast cancer protection.