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The effects of human milk proteins on the proliferation of normal, cancer and cancer stem like cells

  • Kang, Nam Mi (Department of Nursing, Konkuk University) ;
  • Cho, Ssang-Goo (Department of Stem Cell and Regenerative Biotechnology, Konkuk University) ;
  • Dayem, Ahmed Abdal (Department of Stem Cell and Regenerative Biotechnology, Konkuk University) ;
  • Lee, Joohyun (Department of Crop Science, Konkuk University) ;
  • Bae, Seong Phil (Department of Pediatrics, School of Medicine, Soon Chun Hyang University, Seoul Hospital) ;
  • Hahn, Won-Ho (Department of Pediatrics, School of Medicine, Soon Chun Hyang University, Seoul Hospital) ;
  • Lee, Jeong-Sang (Department of Biotechnology and Functional Foods, Jeonju University)
  • Received : 2018.10.15
  • Accepted : 2018.12.03
  • Published : 2018.12.25

Abstract

Human breast milk (HBM) provides neonates with indispensable nutrition. The present study evaluated the anti-cancer activity of diluted and pasteurized early HBM (< 6 weeks' lactation) on human breast cancer cell lines. The cell lines MCF7 and MDA-MB231 were exposed to 1 % HBM from the 1st, 3rd, and 6th weeks of lactation and exhibited reduced proliferation rates. As controls, breast cell lines (293T and MCF-10A), breast cancer cell lines (MCF-7 and MDA-MB-231), and $CD133^{hi}CXCR4^{hi}ALDH1^{hi}$ patient-derived human cancer stem-like cells (KU-CSLCs) were treated with prominent milk proteins ${\beta}$-casein, ${\kappa}$-casein, and lactoferrin at varying doses (10, 50, and $100{\mu}g$) for 24 or 48 hrs. The impact of these proteins on cell proliferation was investigated. Breast cancer cell lines treated with ${\kappa}$-casein and lactoferrin exhibited significantly reduced viability, in both a dose- and time-dependent manner. Interestingly, ${\kappa}$-casein selectively impacted only cancer (but not normal breast) cell lines, particularly the more malignant cell line. However, ${\beta}$-casein-exposed human breast cancer cell lines exhibited a significantly higher proliferation rate. Thus, ${\kappa}$-casein and lactoferrin appear to exert selective anti-cancer activities. Further studies are warranted to determine the mechanisms underlying ${\kappa}$-casein- and lactoferrin-mediated cancer cell-selective cytotoxic effects.

Keywords

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Fig. 1. The cell viabilities of control group and breast cancer cell lines after 24 and 48 hours of incubation periods.

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Fig. 2. The cell viabilities of control group and breast cancer cell lines after 24 and 48 hours of incubation periods.

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Fig. 3. The cell viabilities of control group and breast cancer cell lines after treatment with β-casein, κ-casein, and lactoferrin according to the different cell types and the incubation periods (24 and 48 hours).

References

  1. O. Hallgren, S. Aits, P. Brest, L. Gustafsson, A. K. Mossberg, B. Wullt, and C. Svanborg, Adv. Exp. Med. Biol., 606, 217-240 (2008).
  2. A. do Carmo Franca-Botelho, M. C. Ferreira, J. L. Franca, E. L. Franca, and A. C. Honorio-Franca, Asian. Pac. J. Cancer. Prev., 13(11), 5327-5332 (2012). https://doi.org/10.7314/APJCP.2012.13.11.5327
  3. Y. Zhou, J. Chen, Q. Li, W. Huang, H. Lan, and H. Jiang, Breastfeed. Med., 10(3), 175-182 (2015). https://doi.org/10.1089/bfm.2014.0141
  4. S. S. Hasson, J. Z. Al-Busaidi, Z. A. Al-Qarni, S. Rajapakse, S. Al-Bahlani, M. A. Idris, and T. A. Sallam, Asian. Pac. J. Cancer. Prev., 16(15), 6651-6661 (2015). https://doi.org/10.7314/APJCP.2015.16.15.6651
  5. H. M. Korashy, Z. H. Maayah, A. R. Abd-Allah, A. O. El-Kadi, and A. A. Alhaider, J. Biomed. Biotechnol., 2012, 593195 (2012).
  6. A. K. Leung and R. S. Sauve, J Natl Med Assoc, 97(7), 1010-1019 (2005).
  7. W. H. Hahn, J. H. Song, J. B. Seo, J. E. Lee, J. S. Lee, S. Song, J. Lee, and N. M. Kang, Asia Pac. J. Clin. Nutr., 27(1), 204-210 (2018).
  8. A. Villavicencio, M. S. Rueda, C. G. Turin, and T. J. Ochoa, Biochem. Cell. Biol., 95(1), 12-21 (2017). https://doi.org/10.1139/bcb-2016-0060
  9. Y. Liao, D. Weber, W. Xu, B. P. Durbin-Johnson, B. S. Phinney, and B. Lonnerdal, J. Proteome. Res., 16(11), 4113-4121 (2017). https://doi.org/10.1021/acs.jproteome.7b00486
  10. Y. Zhang, C. F. Lima, and L. R. Rodrigues, Nutr. Rev., 72(12), 763-773 (2014). https://doi.org/10.1111/nure.12155
  11. C. M. Yin, J. H. Wong, J. Xia, and T. B. Ng, Curr. Protein. Pept. Sci., 14(6), 492-503 (2013). https://doi.org/10.2174/13892037113149990066
  12. M. Arias, A. L. Hilchie, E. F. Haney, J. G. Bolscher, M. E. Hyndman, R. E. Hancock, and H. J. Vogel, Biochem. Cell. Biol., 95(1), 91-98 (2017). https://doi.org/10.1139/bcb-2016-0175
  13. J. R. Kanwar, R. K. Kanwar, X. Sun, V. Punj, H. Matta, S. M. Morley, A. Parratt, M. Puri, and R. Sehgal, Curr. Protein. Pept. Sci., 10(4), 308-338 (2009). https://doi.org/10.2174/138920309788922234
  14. P. W. Parodi, Curr. Pharm. Des., 13(8), 813-828 (2007). https://doi.org/10.2174/138161207780363059
  15. M. Zimecki and M. L. Kruzel, J. Exp. Ther. Oncol., 6(2), 89-106 (2007).
  16. R. Jiang and B. Lonnerdal, Biochem. Cell. Biol., 95(1), 99-109 (2017). https://doi.org/10.1139/bcb-2016-0094
  17. H. M. Habib, W. H. Ibrahim, R. Schneider-Stock, and H. M. Hassan, Food. Chem., 141(1), 148-152 (2013). https://doi.org/10.1016/j.foodchem.2013.03.039
  18. D. C. Duarte, A. Nicolau, J. A. Teixeira, and L. R. Rodrigues, J. Dairy. Sci., 94(1), 66-76 (2011). https://doi.org/10.3168/jds.2010-3629
  19. S. H. Gopal and S. K. Das, J Cancer Clin Trials, 1(3), e105 (2016).
  20. M. Kampa, S. Loukas, A. Hatzoglou, P. Martin, P. M. Martin, and E. Castanas, Biochem. J., 319(Pt 3), 903-908 (1996). https://doi.org/10.1042/bj3190903
  21. G. Bonuccelli, R. Castello-Cros, F. Capozza, U. E. Martinez-Outschoorn, Z. Lin, A. Tsirigos, J. Xuanmao, D. Whitaker-Menezes, A. Howell, M. P. Lisanti, and F. Sotgia, Cell. Cycle., 11(21), 3972-3982 (2012). https://doi.org/10.4161/cc.22227
  22. S. W. Park, J. Y. Kim, Y. S. Kim, S. J. Lee, S. D. Lee, and M. K. Chung, World. J. Mens. Health., 32(2), 76-82 (2014). https://doi.org/10.5534/wjmh.2014.32.2.76
  23. O. A. Koval, A. V. Tkachenko, A. S. Fomin, D. V. Semenov, A. A. Nushtaeva, E. V. Kuligina, E. L. Zavjalov, and V. A. Richter, PLoS. One., 9(4), e93921 (2014). https://doi.org/10.1371/journal.pone.0093921
  24. M. J. Oliveira, J. Van Damme, T. Lauwaet, V. De Corte, G. De Bruyne, G. Verschraegen, M. Vaneechoutte, M. Goethals, M. R. Ahmadian, O. Muller, J. Vandekerckhove, M. Mareel, and A. Leroy, Embo. J., 22(22), 6161-6173 (2003). https://doi.org/10.1093/emboj/cdg586
  25. E. R. Sauter, W. Davis, W. Qin, S. Scanlon, B. Mooney, K. Bromert, and W. R. Folk, Biomark. Med., 3(5), 577-588 (2009). https://doi.org/10.2217/bmm.09.46