Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 173903, 9 pages
http://dx.doi.org/10.1155/2014/173903
Research Article

Combined Cytogenotoxic Effects of Bee Venom and Bleomycin on Rat Lymphocytes: An In Vitro Study

1Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
2Animal Wealth Development Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
3Physiology Department, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
4AL-Amodi Autism Research Chair, Autism Research and Treatment Centre, Riyadh, Saudi Arabia

Received 10 January 2014; Accepted 21 March 2014; Published 16 April 2014

Academic Editor: Joohun Ha

Copyright © 2014 Yasmina M. Abd-Elhakim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA: Cancer Journal for Clinicians, vol. 61, no. 2, pp. 69–90, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. L. R. Ferguson and A. E. Pearson, “The clinical use of mutagenic anticancer drugs,” Mutation Research—Fundamental and Molecular Mechanisms of Mutagenesis, vol. 355, no. 1-2, pp. 1–12, 1996. View at Publisher · View at Google Scholar · View at Scopus
  3. R. A. D. Santos and C. S. Takahashi, “Anticlastogenic and antigenotoxic effects of selenomethionine on doxorubicin-induced damage in vitro in human lymphocytes,” Food and Chemical Toxicology, vol. 46, no. 2, pp. 671–677, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Bhanot, R. Sharma, and M. N. Noolvi, “Natural sources as potential anti-cancer agents: a review,” International Journal of Phytomedicine, vol. 3, no. 1, pp. 9–26, 2011. View at Google Scholar · View at Scopus
  5. G. Gajski and V. Garaj-Vrhovac, “Bee venom induced cytogenetic damage and decreased cell viability in human white blood cells after treatment in vitro: a multi-biomarker approach,” Environmental Toxicology and Pharmacology, vol. 32, no. 2, pp. 201–211, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. H. J. Park, S. H. Lee, D. J. Son et al., “Antiarthritic effect of bee venom: inhibition of inflammation mediator generation by suppression of NF-κB through interaction with the p50 subunit,” Arthritis and Rheumatism, vol. 50, no. 11, pp. 3504–3515, 2004. View at Publisher · View at Google Scholar · View at Scopus
  7. D. H. Roh, Y. B. Kwon, H. W. Kim et al., “Acupoint stimulation with diluted bee venom (apipuncture) alleviates thermal hyperalgesia in a rodent neuropathic pain model: involvement of spinal α2-adrenoceptors,” Journal of Pain, vol. 5, no. 6, pp. 297–303, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. D. J. Son, J. W. Lee, Y. H. Lee, H. S. Song, C. K. Lee, and J. T. Hong, “Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds,” Pharmacology and Therapeutics, vol. 115, no. 2, pp. 246–270, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. N. Oršolić, “Bee venom in cancer therapy,” Cancer and Metastasis Reviews, vol. 31, pp. 173–194, 2012. View at Google Scholar
  10. H. Vogel, “Incorporation of melittin into phosphatidylcholine bilayers. Study of binding and conformational changes,” FEBS Letters, vol. 134, no. 1, pp. 37–42, 1981. View at Google Scholar · View at Scopus
  11. X. Liu, D. Chen, L. Xie, and R. Zhang, “Effect of honey bee venom on proliferation of K1735M2 mouse melanoma cells in-vitro and growth of murine B16 melanomas in-vivo,” Journal of Pharmacy and Pharmacology, vol. 54, no. 8, pp. 1083–1089, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. N. Oršolić, L. Šver, S. Verstovšek, S. Terzić, and I. Bašić, “Inhibition of mammary carcinoma cell proliferation in vitro and tumor growth in vivo by bee venom,” Toxicon, vol. 41, pp. 861–870, 2003. View at Publisher · View at Google Scholar
  13. P. J. Russell, D. Hewish, T. Carter et al., “Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies,” Cancer Immunology, Immunotherapy, vol. 53, no. 5, pp. 411–421, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Liu, M. Yu, Y. He et al., “Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway,” Hepatology, vol. 47, no. 6, pp. 1964–1973, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. S. T. Chu, H. H. Cheng, C. J. Huang et al., “Phospholipase A2-independent Ca2+ entry and subsequent apoptosis induced by melittin in human MG63 osteosarcoma cells,” Life Sciences, vol. 80, no. 4, pp. 364–369, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. M. H. Park, M. S. Choi, D. H. Kwak et al., “Anti-cancer effect of bee venomin prostate cancer cells through activation of caspase pathway via inactivation of NF-κB,” Prostate, vol. 71, no. 8, pp. 801–812, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. J. H. Park, Y. J. Jeong, K. K. Park et al., “Melittin suppresses PMA-induced tumor cell invasion by inhibiting NF-κB and AP-1-dependent MMP-9 expression,” Molecules and Cells, vol. 29, no. 2, pp. 209–215, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. G. Gajski and V. Garaj-Vrhovac, “Melittin: a lytic peptide with anticancer properties,” Environmental Toxicolology and Pharmacology, vol. 36, no. 2, pp. 697–705, 2013. View at Publisher · View at Google Scholar
  19. G. Gajski, A. M. Domijan, and V. Garaj-Vrhovac, “Alterations of GSH and MDA levels and their association with bee venom-induced DNA damage in human peripheral blood leukocytes,” Environmental and Molecular Mutagenesis, vol. 53, no. 6, pp. 469–477, 2012. View at Publisher · View at Google Scholar
  20. J. Chen and J. Stubbe, “Bleomycins: towards better therapeutics,” Nature Reviews Cancer, vol. 5, no. 2, pp. 102–112, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Froudarakis, E. Hatzimichael, L. Kyriazopoulou et al., “Revisiting BLM from pathophysiology to safe clinical use,” Critical Reviews in Oncology/Hematology, vol. 87, no. 1, pp. 90–100, 2013. View at Publisher · View at Google Scholar
  22. S. Sleijfer, “Bleomycin-induced pneumonitis,” Chest, vol. 120, no. 2, pp. 617–624, 2001. View at Publisher · View at Google Scholar · View at Scopus
  23. J. Cloos, C. B. A. Reid, M. L. T. van der Sterre et al., “A comparison of bleomycin-induced damage in lymphocytes and primary oral fibroblasts and keratinocytes in 30 subjects,” Mutagenesis, vol. 14, no. 1, pp. 87–93, 1999. View at Publisher · View at Google Scholar · View at Scopus
  24. S. B. Wallach-Dayan, G. Izbicki, P. Y. Cohen, R. Gerstl-Golan, A. Fine, and R. Breuer, “Bleomycin initiates apoptosis of lung epithelial cells by ROS but not by Fas/FasL pathway,” The American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 290, no. 4, pp. L790–L796, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. N. Orsolić, “Potentiation of BLM lethality in HeLa and V79 cells by bee venom,” Archives of Industrial Hygiene and Toxicology, vol. 60, pp. 317–326, 2009. View at Google Scholar
  26. J. O. Schmidt, “Chemistry, pharmacology and chemical ecology of ant venoms,” in Venoms of the Hymenoptera, T. Piek, Ed., pp. 425–508, Academic Press, London, UK, 1986. View at Google Scholar
  27. P. M'Bemba-Meka, N. Lemieux, and S. K. Chakrabarti, “Role of oxidative stress, mitochondrial membrane potential, and calcium homeostasis in nickel sulfate-induced human lymphocyte death in vitro,” Chemico-Biological Interactions, vol. 156, no. 1, pp. 69–80, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. D. I. Bounous, R. P. Campagnoli, and J. Brown, “Comparison of MTT colorimetric assay and tritiated thymidine uptake for lymphocyte proliferation assays using chicken splenocytes,” Avian Diseases, vol. 36, no. 4, pp. 1022–1027, 1992. View at Google Scholar · View at Scopus
  29. G. Fotakis and J. A. Timbrell, “In vitro cytotoxicity assays: comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride,” Toxicology Letters, vol. 160, no. 2, pp. 171–177, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. R. C. Duke and J. J. Cohen, “Morphological and biochemical assays of apoptosis,” in Current Protocols in Immunology, J. E. Coligan and A. M. Kruisbeal, Eds., pp. 1–3, John Wiley & Sons, New York, NY, USA, 1992. View at Google Scholar
  31. W. C. Liles, D. C. Dale, and S. J. Klebanoff, “Glucocorticoids inhibit apoptosis of human neutrophils,” Blood, vol. 86, no. 8, pp. 3181–3188, 1995. View at Google Scholar · View at Scopus
  32. M. K. T. Squier and J. J. Cohen, “Calpain, an upstream regulator of thymocyte apoptosis,” Journal of Immunology, vol. 158, no. 8, pp. 3690–3697, 1997. View at Google Scholar · View at Scopus
  33. K. J. Livak and T. D. Schmittgen, “Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method,” Methods, vol. 25, no. 4, pp. 402–408, 2001. View at Publisher · View at Google Scholar · View at Scopus
  34. D. B. Duncan, “Multiple ranges and multiple F-test,” Biometrics, vol. 11, pp. 1–42, 1995. View at Google Scholar
  35. P. Venkatachalam, V. R. Jayanth, and F. D. Solomon, “Paul modifications of BLM induced cytogenetic damages by 2-deoxy-D-glucose on normal and tumor cells,” International Journal of Human Genetics, vol. 7, pp. 307–314, 2007. View at Google Scholar
  36. M. Jo, M. H. Park, P. S. Kollipara et al., “Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway,” Toxicology and Applied Pharmacology, vol. 258, no. 1, pp. 72–81, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. J. H. Park, K. H. Kim, S. J. Kim, W. R. Lee, K. G. Lee, and K. K. Park, “Bee venom protects hepatocytes from tumor necrosis factor-α and actinomycin D,” Archives of Pharmacal Research, vol. 33, no. 2, pp. 215–223, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. Y. J. Lee, S. J. Kang, B. M. Kim, Y. J. Kim, H. D. Woo, and H. W. Chung, “Cytotoxicity of honeybee (Apis mellifera) venom in normal human lymphocytes and HL-60 cells,” Chemico-Biological Interactions, vol. 169, no. 3, pp. 189–197, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. G. Gajski, T. Cimbora-Zovko, M. Osmak, and V . Garaj-Vrhovac, “Bee venom and melittin are cytotoxic against different types of tumor and non-tumor cell lines in vitro,” Cancer Research Journal, vol. 4, pp. 159–174, 2011. View at Google Scholar
  40. K. H. Kim, Y. S. Kum, Y. Y. Park et al., “The protective effect of bee venom against ethanol-induced hepatic injury via regulation of the mitochondria-related apoptotic pathway,” Basic and Clinical Pharmacology and Toxicology, vol. 107, no. 1, pp. 619–624, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. V. Garaj-Vrhovac and G. Gajski, “Evaluation of the cytogenetic status of human lymphocytes after exposure to a high concentration of bee venom in vitro,” Archives of Industrial Hygiene and Toxicology, vol. 60, no. 1, pp. 27–34, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. Y. Tanaka, S. Takahashi, Y. Mitsui et al., “X-ray Crystallographic and chromatographic characterization of the crystals of Ca2+-calmodulin complexed with bee venom melittin,” Journal of Molecular Biology, vol. 186, no. 3, pp. 675–677, 1985. View at Google Scholar · View at Scopus
  43. B. Weiss and T. L. Wallace, “Mechanism and pharmacological implications of altering calmodulin activity,” in Calcium and Cell Function, W. Y. Cheung, Ed., vol. 1, pp. 329–379, Academic Press, New York, NY, USA, 1980. View at Google Scholar
  44. J. F. Whitfield, A. L. Boynton, J. P. Macmanus, M. Sikorska, and B. K. Tsang, “The regulation of cell proliferation by calcium and cyclic AMP,” Molecular and Cellular Biochemistry, vol. 27, no. 3, pp. 155–179, 1979. View at Google Scholar · View at Scopus
  45. S. J. Hong, G. S. Rim, H. I. Yang et al., “Bee venom induces apoptosis through caspase-3 activation in synovial fibroblasts of patients with rheumatoid arthritis,” Toxicon, vol. 46, no. 1, pp. 39–45, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. D. J. Son, S. J. Ha, H. S. Song et al., “Melittin inhibits vascular smooth muscle cell proliferation through induction of apoptosis via suppression of nuclear factor-κB and Akt activation and enhancement of apoptotic protein expression,” Journal of Pharmacology and Experimental Therapeutics, vol. 317, no. 2, pp. 627–634, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. K. M. Stuhlmeier, “Apis mellifera venom and melittin block neither NF-κB-p50-DNA interactions nor the activation of NF-κB, instead they activate the transcription of proinflammatory genes and the release of reactive oxygen intermediates,” Journal of Immunology, vol. 179, no. 1, pp. 655–664, 2007. View at Google Scholar · View at Scopus
  48. C. L. Ownby, J. R. Powell, M. S. Jiang, and J. E. Fletcher, “Melittin and phospholipase A2 from bee (Apis mellifera) venom cause necrosis of murine skeletal muscle in vivo,” Toxicon, vol. 35, no. 1, pp. 67–80, 1997. View at Publisher · View at Google Scholar · View at Scopus
  49. B. Poddevin, S. Orlowski, J. Belehradek, and L. M. Mir, “Very high cytotoxicity of bleomycin introduced into the cytosol of cells in culture,” Biochemical Pharmacology, vol. 42, pp. S67–S75, 1991. View at Publisher · View at Google Scholar · View at Scopus
  50. S. W. Ip, S. S. Liao, S. Y. Lin et al., “The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells,” In Vivo, vol. 22, no. 2, pp. 237–246, 2008. View at Google Scholar · View at Scopus
  51. G. M. Cohen, “Caspases: the executioners of apoptosis,” Biochemical Journal, vol. 326, no. 1, pp. 1–16, 1997. View at Google Scholar · View at Scopus
  52. W. C. Tu, C. C. Wu, H. L. Hsieh, C. Y. Chen, and S. L. Hsu, “Honeybee venom induces calcium-dependent but caspase-independent apoptotic cell death in human melanoma A2058 cells,” Toxicon, vol. 52, no. 2, pp. 318–329, 2008. View at Publisher · View at Google Scholar · View at Scopus