Food Chemistry 150 (2014) 174

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Letter to the Editor Lunasin: Attenuating effects on tumour growth in systemic malignancies

To the editor Dia et al. have provided interesting data in their recent article (Dia, Frankland-Searby, del Hierro, Garcia, & de Mejia, 2013). Lunasin exerts its anti-neoplastic effects by modulating a number of different pathways in different systemic cancers. For instance, in colo-rectal malignancies it mediates this role in part by virtue of its inhibitory effect on the FAK/ERK/NF-jB pathway (Dia & Gonzalez de Mejia, 2011a). IjB-a expression is typically up-regulated. As a result, increased G2/M phase arrest is seen within the tumor. These changes have recently been confirmed in KM12L4 human colon cancer cell lines. The above effects are initiated following the binding of lunasin to a5b1 integrin. COL12A1 activity is typically accentuated while COL6A1 activity is significantly reduced (Hsieh, Hernandez-Ledesma, Jeong, Park, & de Lumen, 2010). At the same time, FAK activity is attenuated by as much as 60%. p27 expression is markedly up-regulated simultaneously. Similarly, nuclear p50 NF-jB activity is markedly attenuated. Caspase 9 activity is also significantly accentuated. Similarly, clusterin expression is increased by almost 5 times (Dia & Gonzalez de Mejia, 2011b). Lunasin also increases the sensitivity of the tumor cells to other chemotherapeutic agents such as oxaliplatin. It plays this augmenting role primarily by down-regulating PCNA expression within the tumor cells. The combination therapy is also accompanied by increased accentuation of Bax expression along with a simultaneous enhanced down-regulation of Bcl-2 (Jeong, Jeong, Park, et al., 2007). In fact, the Bcl-2/Bax ratio is reduced by almost 95%. In addition, lunasin also augments p21 expression and decreases MMP10 expression within the tumor cells, thus further attenuating tumor progression (Dia & Mejia, 2010). Similar inhibition of tumor growth is seen in mammary malignancies. It mediates its anti-neoplastic role primarily by augmenting p53 independent apoptosis within the primary breast tumor (Pabona, Dave, Su, et al., 2013). This is secondary to its accentuating effect on PTEN expression within the tumor cells which leads to augmented S phase arrest. A negative impact is also seen on H4 acetylation (Hernandez-Ledesma, Hsieh, & de Lumen, 2011). Cyclin 4 expression is also attenuated at the same time. Interestingly, lunasin also augments the sensitivity of breast cancer cells to agents such as aspirin. Aspirin causes G1 phase arrest and thus enhances the pro-apoptotic activity of lunasin. The combination results in marked attenuation of PIK3R1 expression (Chiesa, Rigamonti, Lovati, et al., 2008). Down-regulation of the JUN pathway is also seen which further mitigates tumor growth. At the same time, nuclear localisation of PTEN is significantly augmented. On the other hand, it has a positive impact on non-nuclear localisation of b-catenin. These changes have recently been confirmed in 0308-8146/$ - see front matter Ó 2013 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.foodchem.2013.10.102

MCF-7 as well as MDA-MB-231 cell lines. Besides the above changes, lunasin also enhances extra-nuclear localisation of E cadherin within the tumor cells (Hsieh, Hernandez-Ledesma, & de Lumen, 2010). H3 acetylation is also suppressed at the same time thus further attenuating tumor growth. The above examples clearly illustrate the significant anti-neoplastic effects of lunasin. Further efforts are needed to increase awareness about lunasin and its anti-neoplastic effects amongst physicians especially oncologists. References Chiesa, G., Rigamonti, E., Lovati, M. R., et al (tul=0?>Chiesa et al., 2008). Reduced mammary tumor progression in a transgenic mouse model fed an isoflavonepoor soy protein concentrate. Molecular Nutrition & Food Research, 52, 1121–1129. Dia, V. P., & Gonzalez de Mejia, E. (2011a). Lunasin induces apoptosis and modifies the expression of genes associated with extracellular matrix and cell adhesion in human metastatic colon cancer cells. Molecular Nutrition & Food Research, 55, 623–634. Dia, V. P., & Gonzalez de Mejia, E. (2011b). Lunasin potentiates the effect of oxaliplatin preventing outgrowth of colon cancer metastasis, binds to alpha5beta1 integrin and suppresses FAK/ERK/NF-kappaB signaling. Cancer Letters, 313, 167–180. Dia, V. P., Frankland-Searby, S., del Hierro, F. L., Garcia, G., & de Mejia, E. G. (2013). Structural property of soybean lunasin and development of a method to quantify lunasin in plasma using an optimised immunoassay protocol. Food Chemistry, 138, 334–341. Dia, V. P., & Mejia, E. G. (2010). Lunasin promotes apoptosis in human colon cancer cells by mitochondrial pathway activation and induction of nuclear clusterin expression. Cancer Letters, 295, 44–53. Hernandez-Ledesma, B., Hsieh, C. C., & de Lumen, B. O. (2011). Relationship between lunasin’s sequence and its inhibitory activity of histones H3 and H4 acetylation. Molecular Nutrition & Food Research, 55, 989–998. Hsieh, C. C., Hernandez-Ledesma, B., & de Lumen, B. O. (2010). Lunasin, a novel seed peptide, sensitises human breast cancer MDA-MB-231 cells to aspirinarrested cell cycle and induced apoptosis. Chemico-Biological Interactions, 186, 127–134. Hsieh, C. C., Hernandez-Ledesma, B., Jeong, H. J., Park, J. H., & de Lumen, B. O. (2010). Complementary roles in cancer prevention: Protease inhibitor makes the cancer preventive peptide lunasin bioavailable. PLoS ONE, 5, e8890. Jeong, J. B., Jeong, H. J., Park, J. H., et al (2007). Cancer-preventive peptide lunasin from Solanum nigrum L. inhibits acetylation of core histones H3 and H4 and phosphorylation of retinoblastoma protein (Rb). Journal of Agriculture and Food Chemistry, 55, 10707–10713. Pabona, J. M., Dave, B., Su, Y., et al (2013). 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 & Nutrition, 8, 79–90.



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Lunasin: attenuating effects on tumour growth in systemic malignancies.

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