Anticancer Effect in HL-60 Human Leukemia Cells and Other Helath-Beneficial Functions of Cheese


With regard to the aim of cancer prevention and/or treatment, a considerable number of basic studies have indicated that dairy and other plant-originated natural food products may possess anticancer activity. On the growth of human leukemia cells, for example, enzymatically digested skim milk or fermented milk cultured with various bacteria can exhibit differential suppressive activities. Our research team has previously revealed that highly ripened cheese was capable of demonstrating strong growth inhibition and induction of apoptotic DNA damage on HL-60 human promyelocyticleukemia cells. In this short review, the available information concerning potent anticancer effects of cheese was summarized. From the stand point of Food Science, functional implications for cancer prevention as well as multifaceted function of cheese are discussed.

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S. Yasuda and K. Igoshi, "Anticancer Effect in HL-60 Human Leukemia Cells and Other Helath-Beneficial Functions of Cheese," Open Journal of Blood Diseases, Vol. 3 No. 3A, 2013, pp. 7-10. doi: 10.4236/ojbd.2013.33A002.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] T. Osawa, “Recent Progress of Functional Food Research in Japan,” In: T. Shibamoto, J. Terao and T. Osawa, Eds., Chapter 1, Functional Foods for Disease Prevention II, ACS Symposium Series, ACS Publications, Washington DC, 1998, pp. 2-9.
[2] M. M.Ip, P. A. Masso-Welch and C. Ip, “Prevention of Mammary Cancer with Conjugated Linoleic Acid: Role of the Stroma and the Epithelium,” Journal of Mammary Gland Biology and Neoplasia, Vol. 8, No. 1, 2003, pp. 103-118.
[3] C. Kandaswami, L. T. Lee, P. P. Lee, J. J. Hwang, F. C. Ke, Y. T. Huang and M. T. Lee, “The Antitumor Activities of Flavonoids,” In Vivo, Vol. 19, No. 5, 2005, pp. 895-909.
[4] P. W. Parodi, “A Role for Milk Proteins and Their Peptides in Cancer Prevention,” Current Pharmaceutical Design, Vol. 13, No. 8, 2007, pp. 813-828.
[5] M. Ito, M. K. Roy, K. Kurihara, Y. Watanabe, Y. Kuwabara, S. Nagai and Y. Tamai, “Effects of Bovine Milk Fermented by Culturing with Lactic Acid Bacteria and a Yeast on the Proliferation Activity of Human Carcinoma Cells,” Food Science and Technology International, Vol. 4, No. 2, 1998, pp. 125-129.
[6] M. K. Roy, Y. Watanabe and Y. Tamai, “Induction of Apoptosis in HL-60 Cells by Skimmed Milk Digested with a Proteolytic Enzyme from the Yeast Saccharomyces cerevisiae,” Journal of Bioscience and Bioengineering, Vol. 88, No. 4, 1999, pp. 426-432.
[7] M. K. Roy, Y. Kuwabara, K. Hara, Y. Watanabe and Y. Tamai, “Peptides from the N-Terminal End of Bovine Lactoferrin Induce Apoptosis in Human Leukemic (HL-60) Cells,” Journal of Dairy Science, Vol. 85, No. 9, 2002, pp. 2065-2074.
[8] A. de Moreno de LeBlanc, C. Matar, N. LeBlanc and G. Perdigon, “Effects of Milk Fermented by Lactobacillus helveticus R389 on a Murine Breast Cancer Model,” Breast Cancer Research, Vol. 7, 2005, pp. R477-R486.
[9] J. S. Mader, J. S. Salsman, D. M. Conrad and D. W. Hoskin, “Bovine Lactoferricin Selectively Induces Apoptosis in Human Leukemia and Carcinoma Cell Lines,” Molecular Cancer Therapeutics, Vol. 4, 2005, pp. 612-624.
[10] X. X. Xu, H. R. Jiang, H. B. Li, T. N. Zhuang, G. Zhou and N. Liu, “Apoptosis of Stomach Cancer Cell SGC-7901 and Regulation of Akt Signaling Way Induced by Bovine Lactoferrin,” Journal of Dairy Science, Vol. 93, No. 6, 2010, pp. 2344-2350.
[11] G. D. Birnie, “The HL60 Cell Line: A Model System for Studying Human Myeloid Cell Differentiation,” British Journal of Cancer, Vol. 58, 1988, pp. 41-45.
[12] W. Gorczyca, J. Gong, B. Ardelt, F. Traganos and Z. Darzynkiewicz, “The Cell Cycle Related Differences in Susceptibility of HL-60 cells to Apoptosis Induced by Various Antitumor Agents,” Cancer Research, Vol. 53, No. 13, 1993, pp. 3186-3192.
[13] N. Suh, L. Luyengi, H. H. Fong, A. D. Kinghorn and J. M. Pezzuto, “Discovery of Natural Product Chemopreventive Agents Utilizing HL-60 Cell Differentiation as a Model,” Anticancer Research, Vol. 15, No. 2, 1995, pp. 233-239.
[14] F. Yu, S. Lu, F. Yu, J. P. Shi, M. McGuire and R. Wang, “Cytotoxic Activity of an Octadecenoic Acid Extract from Euphorbia kansui (Euphorbiaceae) on Human Tumor Cell Strains,” Journal of Pharmacy and Pharmacology, Vol. 60, No. 2, 2008, pp. 253-259.
[15] S. Yasuda, N. Ohkura, K. Suzuki, M. Yamasaki, K. Nishiyama, H. Kobayashi, Y. Hoshi, Y. Kadooka and K. Igoshi, “Effects of Highly Ripened Cheeses on HL-60 Human Leukemia Cells: Antiproliferative Activity and Induction of Apoptotic DNA Damage,” Journal of Dairy Science, Vol. 93, No. 4, 2010, pp. 1393-1400.
[16] S. Yasuda, H. Kuwata, K. Kawamoto, J. Shirakawa, S. Atobe, Y. Hoshi, M. Yamasaki, K. Nishiyama, H. Tachibana, K. Yamada, H. Kobayashi and K. Igoshi, “Effect of Highly Lipolyzed Goat Cheese on HL-60 Human Leukemia Cells: Antiproliferative Activity and Induction of Apoptotic DNA Damage,” Journal of Dairy Science, Vol. 95, No. 5, 2012, pp. 2248-2260.
[17] S. Yasuda, K. Kawamoto, T. Hirayama, Y. Kadooka, H. Tachibana, K. Yamada, H. Kobayashi and K. Igoshi, “Induction of Nitric Oxide Generation by Various Cow Milk Cheeses in RAW264.7 Mouse Macrophage-Like Cells,” Milk Science, Vol. 61, No. 2, 2012, pp. 89-94.
[18] E. Kampman, M. L. Slattery, B. Caan and J. D. Potter, “Calcium, Vitamin D, Sunshine Exposure, Dairy Products and Colon Cancer Risk (United States),” Cancer Causes Control, Vol. 11, No. 5, 2000, pp. 459-466.
[19] N. Shinomiya, M. Taniguchi, H. Shimazaki, K. Tanigawa, T. Takemura, M. Tsugita, T. Suzuki and S. Tsuru, “Suppressive Effect on Meth A Tumor Cells by Cheese and Their Derivative Proteins,” Oncologia, Vol. 21, No. 6, 1988, pp. 70-77.
[20] S. Tsuru, N. Shinomiya, M. Taniguchi, H. Shimazaki, K. Tanigawa and K. Nomoto, “Inhibition of Tumor Growth by Dairy Products,” Journal of Clinical and Laboratory Immunology, Vol. 25, No. 4, 1988, pp. 177-183.
[21] M. Phelan and D. Kerins, “The Potential Role of Milk-Derived Peptides in Cardiovascular Disease,” Food and Function, Vol. 2, No. 3-4, 2011, pp. 153-167.
[22] C. M. Urista, R. A. Fernaandez, F. R. Rodriguez, A. A. Cuenca and A. T. Jurado, “Review: Production and Functionality of Active Peptides from Milk,” Food Science and Technology International, Vol. 17, No. 4, 2011, pp. 293-317.
[23] S. Tanabe, S. Tesaki, J. Watanabe, E. Fukushu, K. Sonoyama and J. Kawabata, “Isolation and Structural Elucidation of a Peptide Derived from Edam Cheese that Inhibits Lactoglobulin Transport,” Journal of Dairy Science, Vol. 86, No. 2, 2003, pp. 464-468.
[24] Y. Kudoh, S. Matsuda, K. Igoshi and T. Oki, “Antioxidative Peptide from Milk Fermented with Lactobacillus delbrueckii subsp. bulgaricus IFO13953,”Nippon Shokuhin Kagaku Kaishi, Vol. 48, No. 1, 2001, pp. 44-55.
[25] N. Yamamoto, M. Maeno and T. Takano, “Purification and Characterization of an Antihypertensive Peptide from Yogurt-Like Product Fermented by Lactobacillus helveticus CPN4,”Journal of Dairy Science, Vol. 82, No. 7, 1999, pp. 1388-1393.
[26] K. Igoshi, Y. Kondo, H. Kobayashi, K. Kabata and H. Kawakami, “Antioxidative Activity of Cheese,” Milchwissenschaft, Vol. 63, 2008, pp. 424-426.
[27] K. Kawamoto, K. Igoshi, Y. Kadooka, H. Kobayashi and S. Yasuda, “Scavenging Effects of Commercial Goat Cheeses on Hydrogen Peroxide and Superoxide Anion Radical Assays,” Proceedings of School of Agriculture, Tokai University, Vol. 31, 2012, pp. 31-38.
[28] F. P. Kuhajda, K. Jenner, F. D. Wood, R. A. Hennigar, L. B. Jacobs, J. D. Dick and G. R. Pasternack, “Fatty Acid Synthesis: A Potential Selective Target for Antineoplastic Therapy,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 14, 1994, pp. 6379-6383.
[29] K. Yamada, M. Sasaki and G. Kimura, “Effect of Sodium Butyrate on Actin Distribution in Rat 3Y1 Fibroblasts in Monolayer Culture,” Journal of Cellular Physiology, Vol. 125, 1985, pp. 235-242.
[30] H. Chujo, M. Yamasaki, S. Nou, N. Koyanagi, H. Tachibana and K. Yamada, “Effect of Conjugated Linoleic Acid Isomers on Growth Factor-Induced Proliferation of Human Breast Cancer Cells,” Cancer Letters, Vol. 202, No. 1, 2003, pp. 81-87.
[31] E. Hijova and A. Chmelarova, “Short Chain Fatty Acids and Colonic Health,” Bratislavske Lekarske Listy/Bratislava Medical Journal, Vol. 108, 2007, pp. 354-358.
[32] O. D. Dailey Jr., X. Wang, F. Chen and G. Huang, “Anticancer Activity of Branched-chain Derivatives of Oleic Acid,” Anticancer Research, Vol. 31, No. 10, 2011, pp. 3165-3169.
[33] J. M. W. Wong, R. de Souza, C. W. C. Kendall, A. Emam and D. J. A. Jenkins, “Colonic Health: Fermentation and Short Chain Fatty Acids,” Journal of Clinical Gastroenterology, Vol. 40, No. 3, 2006, pp. 235-243.
[34] R. Havenaar, “Intestinal Health Functions of Colonic Microbial Metabolites: A Review,” Beneficial Microbes, Vol. 2, No. 2, 2011, pp. 103-114.

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