Casein induces the proliferation of bone marrow mononuclear cells, apoptosis of WEHI-3 leukaemic cells and increased survival in a leukaemia mouse model

Ledesma-Martínez,E.; Pérez-Cordero,C.; Córdova-Galaviz,Y.; Sánchez-Tellez,G.; Huerta-Yepez,S.; Aguiñiga-Sánchez,I.; Miranda-Peralta,E.; Monroy-García,A.; Weiss-Steider,B.; Santiago-Osorio,E.

doi:10.3892/ol.2012.758

September 2012 Volume 4 Issue 3

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

September 2012 Volume 4 Issue 3

Full Size Image

Article

Casein induces the proliferation of bone marrow mononuclear cells, apoptosis of WEHI-3 leukaemic cells and increased survival in a leukaemia mouse model

Authors:
- E. Ledesma-Martínez
- C. Pérez-Cordero
- Y. Córdova-Galaviz
- G. Sánchez-Tellez
- S. Huerta-Yepez
- I. Aguiñiga-Sánchez
- E. Miranda-Peralta
- A. Monroy-García
- B. Weiss-Steider
- E. Santiago-Osorio
View Affiliations / Copyright

Affiliations: Hematopoiesis and Leukaemia Laboratory, Research Unit on Cell Differentiation and Cancer, National Autonomous University of Mexico, Mexico City, Mexico, Research Unit in Oncological Diseases, Childhood Hospital of Mexico “Federico Gómez”, Mexico City, Mexico, Cancer Research Unit, Oncology Hospital, Mexico City, Mexico, Immunology and Cancer Laboratory, Medical Research Unit on Oncological Diseases, Mexican Social Security Institute (IMSS), Mexico City, Mexico
Pages: 461-466
|
Published online on: June 14, 2012

https://doi.org/10.3892/ol.2012.758
Expand metrics +

Abstract

Acute myeloid leukaemia results from the neoplastic transformation of haematopoietic stem cells. Although advances have been made in its treatment, the mortality rate remains high. As a result, therapeutic alternatives continue to be explored. In this study, we present evidence that suggests that casein, the principal protein in milk, possesses significant antileukaemic properties. We investigated whether casein inhibited the in vitro proliferation and induced the apoptosis of the mouse myelomonocytic leukaemia cell line WEHI-3. By contrast, under identical conditions, casein markedly promotes the proliferation of mouse normal mononuclear bone marrow cells. Since the selective elimination of leukaemia cells is an ideal therapeutic strategy, we also evaluated the antileukaemic potential of casein in vivo. The results showed that casein increases the survival of mice bearing WEHI-3-induced tumours, suggesting that this molecule is also capable of inhibiting the proliferation of these cells in vivo. The evidence that casein inhibited cell proliferation and induced apoptosis in leukaemia cells in vitro, but increased survival in vivo in a leukaemia mouse model, indicates that casein may be useful in leukaemia therapy.

View Figures

View References

1	Gregory TK, Wald D, Chen Y, Vermaat JM, Xiong Y and Tse W: Molecular prognostic markers for adult acute myeloid leukemia with normal cytogenetics. J Hematol Oncol. 2:23–33. 2009. View Article : Google Scholar : PubMed/NCBI
2	Robak T and Wierzbowska A: Current and emerging therapies for acute myeloid leukemia. Clin Ther. 31:2349–2370. 2009. View Article : Google Scholar : PubMed/NCBI
3	Kuendgen A and Germing U: Emerging treatment strategies for acute myeloid leukemia (AML) in the elderly. Cancer Treat Rev. 35:97–120. 2009. View Article : Google Scholar : PubMed/NCBI
4	Wong CW, Seow HF, Liu AH, Husband AJ, Smithers GW and Watson DL: Modulation of immune responses by bovine beta-casein. Immunol Cell Biol. 74:323–329. 1996. View Article : Google Scholar : PubMed/NCBI
5	Metcalf D, Robb L, Dunn AR, Mifsud S and Di Rago L: Role of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in the development of an acute neutrophil inflammatory response in mice. Blood. 88:3755–3764. 1996.
6	Ramos G, Santiago E, Martínez I, Zambrano I, Manrique B and Weiss B: Sodium caseinate induces differentiation of 32D pluripotential hematopoietic cells. Rev Invest Clin. 52:638–644. 2000.PubMed/NCBI
7	Ramos-Mandujano G, Weiss-Steider B, Melo B, Cordova Y, Ledesma-Martinez E, Bustos S, Silvestre O, Aguiniga I, Sosa N, Martinez I, et al: Alpha-, beta- and kappa caseins inhibit the proliferation of the myeloid cell lines 32D cl3 and WEHI-3 and exhibit different differentiation properties. Immunobiology. 213:133–141. 2008. View Article : Google Scholar
8	Lickliter JD, Wood NJ, Johnson L, McHugh G, Tan J, Wood F, Cox J and Wickham NW: HA14–1 selectively induces apoptosis in Bcl-2-overexpressing leukemia/lymphoma cells, and enhances cytarabine-induced cell death. Leukemia. 17:2074–2080. 2003.
9	Rao J, Xu DR, Zheng FM, Long ZJ, Huang SS, Wu X, Zhou WH, Huang RW and Liu Q: Curcumin reduces expression of Bcl-2, leading to apoptosis in daunorubicin-insensitive CD34⁺ acute myeloid leukemia cell lines and primary sorted CD34⁺ acute myeloid leukemia cells. J Trans Med. 9:71–86. 2011. View Article : Google Scholar : PubMed/NCBI
10	Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 7:57–70. 2000. View Article : Google Scholar
11	Montesinos JJ and Mayani H: New concepts in the biology of acute myeloid leukemia. Gac Med Mex. 138:67–76. 2002.(In Spanish).
12	Tallman MS, Gilliland DG and Rowe JM: Drug therapy for acute myeloid leukemia. Blood. 106:1154–1163. 2005. View Article : Google Scholar : PubMed/NCBI
13	Roboz GJ: Novel approaches to the treatment of acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2011:43–50. 2011. View Article : Google Scholar : PubMed/NCBI
14	Faujan NB, Alitheen SK, Yeap AM, Ali AH, Muhajir FB and Ahmad H: Cytotoxic effect of betulinic acid and betulinic acid acetate isolated from Melaleuca cajuput on human myeloid leukemia (HL-60) cell line. Afr J Biotechnol. 9:6387–6396. 2010.
15	Shipley J and Butera J: Acute myelogenous leukemia. Exp Hematol. 37:649–658. 2009. View Article : Google Scholar
16	He Q and Na X: The effects and mechanisms of a novel 2 aminosteroid on murine WEHI3B leukemia cells in vitro and in vivo. Leuk Res. 25:455–461. 2001. View Article : Google Scholar : PubMed/NCBI
17	Yoon JS, Kim JY, Park HK, Kim ES, Ahn KS, Yoon SS, Cho CG, Kim BK and Lee YY: Antileukemic effect of a synthetic vitamin D3 analog, HY-11, with low potential to cause hypercalcemia. Int J Oncol. 32:387–396. 2008.PubMed/NCBI
18	Majeti R: Monoclonal antibody therapy directed against human acute myeloid leukemia stem cells. Oncogene. 30:1009–1019. 2010. View Article : Google Scholar : PubMed/NCBI
19	Noursadeghi M, Bickerstaff MCM, Herbert J, Moyes D, Cohen J and Pepys MB: Production of granulocyte colony-stimulating factor in the nonspecific acute phase response enhances host resistance to bacterial infection. J Immunol. 169:913–919. 2002. View Article : Google Scholar
20	Russell MW, Brooker BE and Reiter B: Electron microscopic observations of the interaction of casein micelles and milk fat globules with bovine polymorphonuclear leucocytes during the phagocytosis of staphylococci in milk. J Comp Pathol. 87:43–52. 1977. View Article : Google Scholar
21	Chabance B, Marteau P, Rambaud J, Migliore D, Boynard M, Perrotin P, Jollès P and Fiat AM: Casein peptide release and passage to the blood in humans during digestion of milk or yogurt. Biochimie. 80:155–165. 1998. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Casein induces the proliferation of bone marrow mononuclear cells, apoptosis of WEHI-3 leukaemic cells and increased survival in a leukaemia mouse model

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Related Articles