In vitro cytotoxic and genotoxic effects of donkey milk on lung cancer and normal cells lines

https://doi.org/10.17221/221/2018-CJFSCitation:Akca C., Vatan O., Yilmaz D., Huriyet H., Cinkilic N., Cavas T. (2019): In vitro cytotoxic and genotoxic effects of donkey milk on lung cancer and normal cells lines. Czech J. Food Sci., 37: 29-35.
download PDF

In vitro cytotoxic and genotoxic effects of donkey milk on cancer (A549) and normal (BEAS-2B) lung cell lines were investigated. The XTT and WST-1 tests as well as clonogenic assays were used to evaluate cytotoxicity. The comet assay and micronucleus test were used as genotoxicity endpoints. Donkey milk showed lower cytotoxic effects against normal lung cell line BEAS-2B in comparison to the tumor cell line A549. Genotoxicity experiments revealed dose dependent increases in the frequencies of micronuclei and single stranded DNA breaks in A549 cells whereas no significant damage was observed in BEAS-2B cells. The results indicate that donkey milk has anti-proliferative and genotoxic effects on lung cancer cells at concentrations which are non-toxic to normal lung cells.

References:
References
 
Al Ahmad Mahmoud, Al Natour Zeina, Mustafa Farah, Rizvi Tahir A. (2018): Electrical Characterization of Normal and Cancer Cells. IEEE Access, 6, 25979-25986  https://doi.org/10.1109/ACCESS.2018.2830883
 
Amati L., Marzulli G., Martulli M., Tafaro A., Jirillo F., Pugliese V., Martemucci G., D'Alessandro A., Jirillo E. (2010): Donkey and Goat Milk Intake and Modulation of the Human Aged Immune Response. Current Pharmaceutical Design, 16, 864-869  https://doi.org/10.2174/138161210790883651
 
Anandhini B., Palaniswamy M. (2013): Anticancer effect of goat milk fermented by Lactobacillus plantarum and Lactobacillus paracasei. International Journal of Pharmacy and Pharmaceutical Sciences, 5(3): 813–828.
 
ARAYA C, LOMONTE B (2007): Antitumor effects of cationic synthetic peptides derived from Lys49 phospholipase A2 homologues of snake venoms. Cell Biology International, 31, 263-268  https://doi.org/10.1016/j.cellbi.2006.11.007
 
Çavaş Tolga, Çinkılıç Nilüfer, Vatan Özgür, Yılmaz Dilek (2014): Effects of fullerenol nanoparticles on acetamiprid induced cytoxicity and genotoxicity in cultured human lung fibroblasts. Pesticide Biochemistry and Physiology, 114, 1-7  https://doi.org/10.1016/j.pestbp.2014.07.008
 
Chiofalo Biagina, Dugo Paola, Bonaccorsi Ivana L., Mondello Luigi (2011): Comparison of major lipid components in human and donkey milk: new perspectives for a hypoallergenic diet in humans. Immunopharmacology and Immunotoxicology, 33, 633-644  https://doi.org/10.3109/08923973.2011.555409
 
Clementi Emily A., Wilhelm Kristina R., Schleucher Jürgen, Morozova-Roche Ludmilla A., Hakansson Anders P., Netto Luis Eduardo Soares (2013): A Complex of Equine Lysozyme and Oleic Acid with Bactericidal Activity against Streptococcus pneumoniae. PLoS ONE, 8, e80649-  https://doi.org/10.1371/journal.pone.0080649
 
Cunsolo Vincenzo, Saletti Rosaria, Muccilli Vera, Foti Salvatore (2007): Characterization of the protein profile of donkey's milk whey fraction. Journal of Mass Spectrometry, 42, 1162-1174  https://doi.org/10.1002/jms.1247
 
Ertel A., Verghese A., Byers S.W., Ochs M., Tozeren A. (2006): Pathway-specific differences between tumor cell lines and normal and tumor tissue cells. Molecular Cancer, 5: 55. https://doi.org/10.1186/1476-4598-5-55
 
Fang Bing, Zhang Ming, Tian Mai, Jiang Lu, Guo Hui Yuan, Ren Fa Zheng (2014): Bovine lactoferrin binds oleic acid to form an anti-tumor complex similar to HAMLET. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1841, 535-543  https://doi.org/10.1016/j.bbalip.2013.12.008
 
Fantuz F., Vincenzetti S., Polidori P., Vita A., Polidori F., Salimei E. (2001): Study on the protein fractions of donkey milk. In: Proceedings of the XIV A.S.P.A. Congress. Firenze, Italy: 635–637.
 
Furlong Suzanne J., Mader Jamie S., Hoskin David W. (2010): Bovine lactoferricin induces caspase-independent apoptosis in human B-lymphoma cells and extends the survival of immune-deficient mice bearing B-lymphoma xenografts. Experimental and Molecular Pathology, 88, 371-375  https://doi.org/10.1016/j.yexmp.2010.02.001
 
Ganjam L.S., Thornton W.H., Marshall R.T., MacDonald R.S. (1997): Antiproliferative Effects of Yogurt Fractions Obtained by Membrane Dialysis on Cultured Mammalian Intestinal Cells. Journal of Dairy Science, 80, 2325-2329  https://doi.org/10.3168/jds.S0022-0302(97)76183-6
 
Gill Harsharnjit S., Cross M. L. (2000): Anticancer properties of bovine milk. British Journal of Nutrition, 84, -  https://doi.org/10.1017/S0007114500002397
 
Habib Hosam M., Ibrahim Wissam H., Schneider-Stock Regine, Hassan Hassan M. (2013): Camel milk lactoferrin reduces the proliferation of colorectal cancer cells and exerts antioxidant and DNA damage inhibitory activities. Food Chemistry, 141, 148-152  https://doi.org/10.1016/j.foodchem.2013.03.039
 
Host A. (2002): Frequency of cow’s milk allergy in childhood. Annals of Allergy, Asthma & Immunology, 89: 33–337.
 
Huang Yibing, Feng Qi, Yan Qiuyan, Hao Xueyu, Chen Yuxin (2015): Alpha-Helical Cationic Anticancer Peptides: A Promising Candidate for Novel Anticancer Drugs. Mini-Reviews in Medicinal Chemistry, 15, 73-81  https://doi.org/10.2174/1389557514666141107120954
 
Korashy Hesham M., Maayah Zaid H., Abd-Allah Adel R., El-Kadi Ayman O. S., Alhaider Abdulqader A. (2012): Camel Milk Triggers Apoptotic Signaling Pathways in Human Hepatoma HepG2 and Breast Cancer MCF7 Cell Lines through Transcriptional Mechanism. Journal of Biomedicine and Biotechnology, 2012, 1-9  https://doi.org/10.1155/2012/593195
 
Kumbıçak Ümit, Çavaş Tolga, Çinkılıç Nilüfer, Kumbıçak Zübeyde, Vatan Özgür, Yılmaz Dilek (2014): Evaluation of in vitro cytotoxicity and genotoxicity of copper–zinc alloy nanoparticles in human lung epithelial cells. Food and Chemical Toxicology, 73, 105-112  https://doi.org/10.1016/j.fct.2014.07.040
 
Laursen I., Briand P., Lykkesfeldt A.E. (1990): Serum albumin as a modulator on growth of the human breast cancer cell line MCF-7. Anticancer Research, 10: 343–351.
 
Lionetti L., Cavaliere G., Bergamo P., Trinchese G., De Filippo C., Gifuni G., Gaita M., Pignalosa A., Donizzetti I., Putti R., Di Palo R., Barletta A., Mollica M.P. (2012): Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and anti-inflammatory defenses in rats. Molecular Nutrition & Food Research, 56: 1596–1600.
 
Lopez-Exposito I., Recio I. (2008): Protective effect of milk peptides: Antibacterial and antitumor proteins. Advances in Experimental Medicine and Biology, 606: 271–293.
 
Ma Jieqing, Guan Rongfa, Shen Haitao, Lu Fei, Xiao Chaogeng, Liu Mingqi, Kang Tianshu (2013): Comparison of anticancer activity between lactoferrin nanoliposome and lactoferrin in Caco-2 cells in vitro. Food and Chemical Toxicology, 59, 72-77  https://doi.org/10.1016/j.fct.2013.05.038
 
Mader J. S. (2005): Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines. Molecular Cancer Therapeutics, 4, 612-624  https://doi.org/10.1158/1535-7163.MCT-04-0077
 
Mahanta Sailendra, Paul Subhankar (2015): Stable Self-Assembly of Bovine α-Lactalbumin Exhibits Target-Specific Antiproliferative Activity in Multiple Cancer Cells. ACS Applied Materials & Interfaces, 7, 28177-28187  https://doi.org/10.1021/acsami.5b06076
 
Malihe Shariatikia M., Behbahani M., Mohabatkar H. (2017): Anticancer activity of cow, sheep, goat, mare, donkey and camel milks and their caseins and whey proteins and in silico comparison of the caseins. Molecular Biology Research Communications, 6: 57–64.
 
Mao Xueying, Gu Junnan, Sun Yan, Xu Shiping, Zhang Xiaoying, Yang Haiying, Ren Fazheng (2009): Anti-proliferative and anti-tumour effect of active components in donkey milk on A549 human lung cancer cells. International Dairy Journal, 19, 703-708  https://doi.org/10.1016/j.idairyj.2009.05.007
 
Nielsen Søren B., Wilhelm Kristina, Vad Brian, Schleucher Jürgen, Morozova-Roche Ludmilla A., Otzen Daniel (2010): The Interaction of Equine Lysozyme:Oleic Acid Complexes with Lipid Membranes Suggests a Cargo Off-Loading Mechanism. Journal of Molecular Biology, 398, 351-361  https://doi.org/10.1016/j.jmb.2010.03.012
 
Parodi P. (2007): A Role for Milk Proteins and their Peptides in Cancer Prevention. Current Pharmaceutical Design, 13, 813-828  https://doi.org/10.2174/138161207780363059
 
Pepe Giacomo, Tenore Gian Carlo, Mastrocinque Raffaella, Stusio Paola, Campiglia Pietro (2013): Potential Anticarcinogenic Peptides from Bovine Milk. Journal of Amino Acids, 2013, 1-7  https://doi.org/10.1155/2013/939804
 
Polidori P., Vincenzetti S. (2012): Protein profile characterization of donkey milk. In: Hurley W. (ed.): Milk Protein. IntechOpen: 215–232.
 
Praveesh B.V., Angayarkanni J., Palaniswamy M. (2011): Antihypertensive and anticancer effect of cow milk fermented by Lactobacillus plantarum and Lactobacillus paracasei. International Journal of Pharmacy and Pharmaceutical Sciences, 3: 452–456.
 
Salwa M. Quita, Lina A.F. Kurdi (2010): Antigenotoxic and anticytotoxic effect of camel milk in mice treated with cisplatin. Saudi Journal of Biological Sciences, 17, 159-166  https://doi.org/10.1016/j.sjbs.2010.02.010
 
Rahmat A., Rosli R., Hoon T.M., Umar-Tsafe N., Ali A.M., Abu Bakar M.F. (2006): Comparative evaluation of cytotoxic effects of milk from various species on leukemia cell lines. Malaysian Journal Of Medicine And Health Sciences, 2: 1–10.
 
Sah B. N. P., Vasiljevic T., McKechnie S., Donkor O. N. (2015): Identification of Anticancer Peptides from Bovine Milk Proteins and Their Potential Roles in Management of Cancer: A Critical Review. Comprehensive Reviews in Food Science and Food Safety, 14, 123-138  https://doi.org/10.1111/1541-4337.12126
 
Sternhagen L.G., Allen J.C. (2001): Growth rates of a human colon adenocarcinoma cell line are regulated by the milk protein alpha-lactalbumin. Advances in Experimental Medicine and Biology, 50: 115–120.
 
Singh Narendra P., McCoy Michael T., Tice Raymond R., Schneider Edward L. (1988): A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental Cell Research, 175, 184-191  https://doi.org/10.1016/0014-4827(88)90265-0
 
Svensson Malin, Sabharwal Hemant, Håkansson Anders, Mossberg Ann-Kristin, Lipniunas Peter, Leffler Hakon, Svanborg Catharina, Linse Sara (1999): Molecular Characterization of α–Lactalbumin Folding Variants That Induce Apoptosis in Tumor Cells. Journal of Biological Chemistry, 274, 6388-6396  https://doi.org/10.1074/jbc.274.10.6388
 
Szachowicz-Petelska B., Dobrzynska I., Sulkowski S., Figaszewski Z.A. (2010): Characterization of the cell membrane during cancer transformation. Journal of Environmental Biology, 31: 845–850.
 
Wilhelm Kristina, Darinskas Adas, Noppe Wim, Duchardt Elke, Mok K. Hun, Vukojević Vladana, Schleucher Jürgen, Morozova-Roche Ludmilla A. (2009): Protein oligomerization induced by oleic acid at the solid-liquid interface - equine lysozyme cytotoxic complexes. FEBS Journal, 276, 3975-3989  https://doi.org/10.1111/j.1742-4658.2009.07107.x
 
Wise Sandra S., Holmes Amie L., Qin Qin, Xie Hong, Katsifis Spiros P., Thompson W. Douglas, Wise John Pierce (2010): Comparative Genotoxicity and Cytotoxicity of Four Hexavalent Chromium Compounds in Human Bronchial Cells. Chemical Research in Toxicology, 23, 365-372  https://doi.org/10.1021/tx900363j
 
Yoo Yung-Choon, Watanabe Ryosuke, Koike Yuko, Mitobe Manabu, Shimazaki Kei-ichi, Watanabe Sikiko, Azuma Ichiro (1997): Apoptosis in Human Leukemic Cells Induced by Lactoferricin, a Bovine Milk Protein-Derived Peptide: Involvement of Reactive Oxygen Species. Biochemical and Biophysical Research Communications, 237, 624-628  https://doi.org/10.1006/bbrc.1997.7199
 
Zhang Yunlei, Lima Cristovao F., Rodrigues Ligia R. (2015): In vitro evaluation of bovine lactoferrin potential as an anticancer agent. International Dairy Journal, 40, 6-15  https://doi.org/10.1016/j.idairyj.2014.08.016
 
download PDF

© 2020 Czech Academy of Agricultural Sciences