Co-administration of amygdalin and deoxynivalenol disrupted regulatory proteins linked to proliferation of porcine ovarian cells in vitro


  • Marek Halenár Slovak University of Agriculture, Faculty of Biotechnology and Food Sciences, Department of Animal Physiology, Tr. A. Hlinku 2, 949 76 Nitra
  • Marí­na Medveďová Slovak University of Agriculture, Faculty of Biotechnology and Food Sciences, Department of Animal Physiology, Tr. A. Hlinku 2, 949 76 Nitra
  • Simona Baldovská Slovak University of Agriculture, Faculty of Biotechnology and Food Sciences, Department of Animal Physiology, Tr. A. Hlinku 2, 949 76 Nitra
  • Katarí­na Michalcová Slovak University of Agriculture, Faculty of Biotechnology and Food Sciences, Department of Animal Physiology, Tr. A. Hlinku 2, 949 76 Nitra
  • Adriana Kolesárová Slovak University of Agriculture, Faculty of Biotechnology and Food Sciences, Department of Animal Physiology, Tr. A. Hlinku 2, 949 76 Nitra



amygdalin, deoxynivalenol, ovarian cell, proliferation, apoptosis


Deoxynivalenol (DON) represents one of the most prevalent trichothecene mycotoxin produced by Fusarium species, causing economic and health impacts. On the other hand, amygdalin has been demonstrated to possess both prophylactic and curative properties, thus it has been used as a traditional drug because of its wide range of medicinal benefits, including curing or preventing cancer, relieving fever, suppressing cough, and quenching thirst. The aim of this in vitro study was to evaluate potential effects of natural product amygdalin combined with mycotoxin deoxynivalenol (DON) on the key regulators of cell proliferation and apoptosis in porcine ovarian granulosa cells. Ovarian granulosa cells were incubated for 24h with amygdalin (1, 10, 100, 1000, 10 000 μg.mL-1) combined with deoxynivalenol (1 μg.mL-1), while the control group remained untreated. The presence of proliferative (cyclin B1, PCNA) and apoptotic markers (caspase-3) in porcine ovarian granulosa cells after amygdalin treatment (1, 10, 100, 1000, 10 000 μg.mL-1) combined with deoxynivalneol (1 μg.mL-1) was detected by immunocytochemistry. The presence of proliferative (cyclin B1, PCNA) and apoptotic markers (caspase-3) in porcine ovarian granulosa cells was detected by immunocytochemistry. Co-administration of amygdalin plus DON significantly (p <0.05) increased the number of granulosa cells containing cyclin B1 and PCNA at all tested concetrations, when compared to control. However, percentage of granulosa cells containing major apoptotic marker caspase-3 did not differ after co-administration of amygdalin and DON. In summary, results form this in vitro study indicate that co-exposure of amygdalin and deoxynivalenol  may act to stimulate proliferation-associated peptides in porcine ovarian granulosa cells, and thus alter cell proliferation and normal follicular development.


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Alassane-Kpembi, I., Puel, O., Oswald, I. P. 2015. Toxicological interactions between the mycotoxins deoxynivalenol, nivalenol and their acetylated derivatives in intestinal epithelial cells. Archives of Toxicology, vol. 89, no. 8, p. 1337-1346. PMid:25033990

Arunachalam, C., Doohan, F. M. 2013. Trichothecene toxicity in eukaryotes: cellular and molecular mechanisms in plants and animals. Toxicology Letters, vol. 217, no. 2, p. 149-158. PMid:23274714

Bromley, J., Hughes, B. G., Leong, D. C., Buckley, N. A. 2005. Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C. Annals of Pharmacotherapy, vol. 39, no. 9, p. 1566-1569. PMid:16014371

Caloni, F., Ranzenigo, G., Cremonesi, F., Spicer, L. J. 2009. Effects of trichothecene, T-2 toxin, on proliferation and steroid production by GCs. Toxicon, vol. 54, no. 3, p. 337-344. PMid:19463844

Cortinovis, C., Caloni F., Schreiber N. B., Spicer L. J. 2014. Effects of fumonisin B1 alone and combined with deoxynivalenol or zearalenone on porcine granulosa cell proliferation and steroid production. Theriogenology, vol. 81, no. 8, p. 1042-1049. PMid:24576714

Dänicke, S. 2002. Fusarium toxins in animal nutrition (Fusarium-toxine in der Tierernährung). Grosstierpraxis, vol. 3, p. 5-18.

Denault, J. B., Salvesen, G. S. 2008. Apoptotic caspase activation and activity. Methods in Molecular Biology, vol. 414, p. 191-220.

Deng, Y., Guo, Z. G., Zeng, Z. L., Wang, Z. 2002. Studies on the pharmacological effects of saffron (Crocus sativus L.). Zhongguo Zhong Yao Za Zhi, vol. 27, no. 8, p. 565-568. PMid:12776492

Desjardins, A. E. 2009. From yellow rain to green wheat: 25 years of trichothecene biosynthesis research. Journal of Agricultural and Food Chemistry, vol. 57, no. 11, p. 4478-4484. PMid:19385595

Fukuda, T., Ito, H., Mukainaka, T., Tokuda, H., Nishino, H., Yoshida, T. 2003. Anti-tumor promoting effect of glycosides from Prunus persica seeds. Biological and Pharmaceutical Bulletin, vol. 26, no. 2, p. 271-273. PMid:12576693

Halenár, M., Medveďová, M., Maruniaková, N., Kolesárová, A. 2015. Assessment of a potential preventive ability of amygdalin in mycotoxin-induced ovarian toxicity. Journal of Environmental Science and Health B, vol. 50, no. 6, p. 411-416. PMid:25844862

Howard-Ruben, J., Miller, N. J. 1984. Unproven methods of cancer management. Part II: Current trends and implications for patient care. Oncology Nursing Forum, vol. 11, no.1, p. 67-73. PMid:6318190

Chandler, R. F., Anderson, L. A., Phillipson, J. D. 1984. Laetrile in perspective. Canadian Pharmacists Journal, vol. 117, p. 517-520.

Chang, H. K., Shin, M. S., Yang, H. Y., Lee, J. W., Kim, Y. S., Lee, M. H., Kim, J., Kim, K. H., Kim, C. J. 2006. Amygdalin Induces Apoptosis through Regulation of Bax and Bcl-2 Expressions in Human DU145 and LNCaP Prostate Cancer Cells. Biological and Pharmaceutical Bulletin, vol. 29, no. 8, p. 1597-1602. PMid:16880611

Kolesárová, A., Sirotkin, A. V., Kováčik, J. 2008. Endocrine and intracellular mechanisms of sexual gestation of gilts (Endokrinné a vnútrobunkové mechanizmy pohlavného dospievania prasničiek). 1st ed. Nitra, Slovakia : Slovak University of Agriculture, p. 131. ISBN 978-80-552-0109-2.

Kolesarova, A., Capcarova, M., Maruniakova, N., Lukac, N., Ciereszko, R. E., Sirotkin, A. V. 2012. Resveratrol Inhibits Reproductive Toxicity Induced by Deoxynivalenol. Journal of Environmental Science and Health Part B, vol. 47, no. 9, p. 1329-1334. PMid:22540658

Kolesarova, A., Sirotkin, A. V., Mellen, M., Roychoudhury, S. 2015. Possible intracellular regulators of female sexual maturation. Physiological research, vol. 64, no. 3, p. 379-386. PMid:25536325

Kovacova, V., Omelka, R., Sarocka, A., Sranko, P., Adamkovicova, M., Toman, R., Halenar, M., Kolesarova, A., Martiniakova, M. 2016. Potravinarstvo, vol. 10, no. 1, p. 393-399.

Larsen, J. C., Hunt, J., Perrin, I., Ruckenbauer, P. 2004. Workshop on trichothecenes with a focus on DON: summary report. Toxicology Letters, vol. 153, no. 1, p. 1-22. PMid:15342076

Lee, H. M., Moon, A. 2016. Amygdalin regulates apoptosis and adhesion in Hs578T Triple-Negative Breast Cancer Cells. Biomolecules & Therapeutics (Seoul), vol. 24, no. 1, p. 62-66. PMid:26759703

Makarević, J., Rutz, J., Juengel, E., Kaulfuss, S., Reiter, M., Tsaur, I., Bartsch, G., Haferkamp, A., Blaheta, R. A. 2014. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyklin A and cdk2. PLoS ONE, vol. 9, no. 8, p. 1-9. PMid:25136960

Makarević, J., Juengel, E., Tsaur, I., Borgmann, H., Nelson, K., Thomas, C., Bartsch, G., Haferkamp, A., Blaheta, R. A. 2016. Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro. Life Sciences, vol. 147, p. 137-142. PMid:26827990

Maruniakova, N., Kadasi, A., Sirotkin, A. V., Bulla, J., Kolesarova, A. 2014. T-2 toxin and its metabolite HT-2 toxin combined with insuin-like growth factor-I modify progesterone secretion by porcine ovarian granulosa cells. Journal of Environmental Science and Health Part A, vol. 49, no. 4, p. 404-409. PMid:24345238

Medvedova, M., Kolesarova, A., Capcarova, M., Labuda, R., Sirotkin, A. V., Kovacik, J., Bulla, J. 2011. The effect of deoxynivalenol on the secretion activity, proliferation and apoptosis of porcine ovarian granulosa cells in vitro. Journal of Environmental Science and Health, vol. 46, no.3, p. 213-219. PMid:21442537

Moertel, C. G., Fleming, T. R., Rubin, J. A. 1982. Clinical trial of amygdalin in the treatment of human cancer. The New England Journal of Medicine, vol. 306, no. 4, p. 201-206. PMid:7033783

Naryzhny, S. N., Lee, H. 2001. Protein profiles of the Chinese hamster ovary cells in the resting and proliferating stages. Electrophoresis, vol. 22, no. 9, p. 1764-1775.<1764::AID-ELPS1764>3.0.CO;2-V

Oyewole, O. I., Olayinka, E. T. 2009. Hydroxocobalamin (vitb12a) effectively reduced extent of cyanide poisoning arising from oral amygdalin ingestion in rats. Journal of Toxicology and Environmental Health Sciences, vol. 1, no. 1, p. 8-11.

Parent-Massin, D. 2004. Haematotoxicity of trichothecenes. Toxicology Letters, vol. 153, no. 1, p. 75-81. PMid:15342083

Pestka, J. J., Zhou, H. R., Moon, Y., Chung, Y. J. 2004. Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox. Toxicology Letters, vol. 153, no. 1, p. 61-73. PMid:15342082

Pestka, J. J., Smolinski, A.T. 2005. Deoxynivalenol: toxicology and potential effects on humans. Journal of Toxicology and Environmental Health. Part B, Critical Reviews, vol. 8, no. 1, p. 39-69. PMid:15762554

Porter, A. G., Jänicke, R. U. 1996. Emerging roles of caspase-3 in apoptosis. Cell Death and Differentiation, vol. 6, no. 2, p. 99-104. PMid:10200555

Petro, E. M., Leroy, J. L., Van Cruchten, S. J., Covaci, A., Jorssen, E. P., Bols, P. E. 2012. Endocrine disruptors and female fertility: focus on (bovine) ovarian follicular physiology. Theriogenology, vol. 78, no. 9, p. 1887-1900. PMid:22925646

Ranzenigo, G., Caloni, F., Cremonesi, F., Aad, P. Y., Spicer, L. J. 2008. Effects of Fusarium mycotoxins on steroid production by porcine GCs. Animal Reproduction Science, vol. 107, no. 1-2, p. 115-130. PMid:17656051

Rauws, A. G., Olling, M., Timmerman, A. 1982. The pharmacokinetics of prunasin, a metabolite of amygdalin. Journal of Toxicology. Clinical Toxicology, vol. 19, no. 8, p. 851-856. PMid:7182513

Rawan, A. F., Yoshioka, S., Abe, H., Acosta, T. J. 2015. Insulin-like growth factor-1 regulates the expression of luteinizing hormone receptor and steroid production in bovine granulosa cells. Reproduction in Domestic Animals, vol. 50, no. 2, p. 283-91. PMid:25626338

Song, Z., Xu, X. 2014. Advanced research on anti-tumor effects of amygdalin. Journal of Cancer Resesarch & Therapy, vol. 1, p. 3-7.

Spicer, L. J., Alonso, J., Chamberlain, C. S. 2001. Effects of Thyroid Hormones on Bovine Granulosa and Thecal Cell Function In Vitro: Dependence on Insulin and Gonadotropins. Journal of Dairy Science. vol. 84, no. 5, p. 1069-1076.

Strugala, G. J., Stahl, R., Elsenhans, B., Rauws, A. G., Forth, W. 1995. Small-intestinal transfer mechanism of prunasin, the primary metabolite of the cyanogenic glycoside amygdalin. Human Experimental Toxicology, vol. 14, no. 11, p. 895-901. PMid:8588951

Tomanek, M., Chronowska, E. 2006. Immunohistochemical localization of proliferating cell nuclear antigen (PCNA) in the pig ovary. Folia Histochemica et Cytobiologica, vol. 44, no. 4, p. 269-274. PMid:17219721

Vejdovszky, K., Schmidt, V., Warth, B., Marko, D. 2016. Combinatory estrogenic effects between the isoflavone genistein and the mycotoxins zearalenone and alternariol in vitro. Molecular Nutrition & Food Research, vol. 61, no. 3, p. 1-12.

Yidirim, F. A., Askin, M. A. 2010. Variability of amygdalin content in seeds of sweet and bitter apricot cultivars in Turkey. African Journal of Biotechnology, vol.9, no. 39, p. 6522-6524.

Zhou, C., Qian, L., Ma, H., Yu, X., Zhang, Y., Qu, W., Zhang, X., Xia, W. 2012. Enhancement of amygdalin activated with β-D-glucosidase on HepG2 cells proliferation and apoptosis. Carbohydrate Polymers, vol. 90, no. 1, p. 516-523. PMid:24751072

Zhu, L., Yuan, H., Guo, Ch., Lu, Y., Deng, S., Yang,Y., Wei,Q., Wen, L., He, Z. 2012. Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a caspase-3- and caspase-9-dependent mitochondrial signaling pathway. Journal of Cellular Physiology, vol. 227, no. 5, p. 1814-1820. PMid:21732350




How to Cite

Halenár, M. ., Medveďová, M. ., Baldovská, S. ., Michalcová, K. ., & Kolesárová, A. . (2017). Co-administration of amygdalin and deoxynivalenol disrupted regulatory proteins linked to proliferation of porcine ovarian cells in vitro. Potravinarstvo Slovak Journal of Food Sciences, 11(1), 503–509.

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