28Feb 2017

EVALUATION OF ANTICANCER ACTIVITY OF SOME VENOMOUS ANIMAL TOXINS ON HUMAN BREAST AND COLON CANCER CELL LINES AND RELATED ANTIOXIDANT PROFILE

  • Department of Zoology, Faculty of girl for science and art, Ain Shams University, Naser City, Cairo, Egypt.
  • R&D Sector, The Holding Company for Production of Vaccines, Sera and Drugs (VACSERA), Dokky, Giza, Egypt.
  • Department of Zoology, Faculty of science, Professor of physiology and Director of Genetic Engineering Center, Al-Azhar University, Naser City, Cairo, Egypt.
  • Department of Zoology, Faculty of girl for science and art, Professor of Cytogenetic and Director of Zoology department, Ain Shams University, Naser City, Cairo, Egypt.
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Background:- Breast and colon cancers are the most types of cancer in Egyptian patients. Radiation and chemotherapy have undesirable side effects, so the drugs are used instead. Venoms have been used as folk medicine since ancient times. Purpose and aim:- This study examines the anticancer potential of Egyptian snake (Naja haje), scorpion (Leiurus quinquestriatus) and bee (Apis mellifera) venoms then compared to a synthetic anticancer drug 5-Flurouracil (5-FU). Methods:- The cytotoxicity activity of tested venoms was determined using SRB assay. Antioxidant potential was determined by the evaluation of the variation in MDA, NO. and GSH content. RNA was extracted to evaluate the expression of P53, Bcl2 and Bax genes using semi-quantitative RT-PCR analysis after 24hrs. treatment. Results & Discussion:- MCF-7 cells were more sensitive than Caco-2 cells to tested venoms while 5-FU was more toxic to both cell lines. The Naja h., Leiurus q. and Apis m. venoms had IC50 as 3.5, 27.8 and 2.5 µg/ml with MCF-7 cell line and 20, 32.3 and 14 µg/ml with Caco-2 cell line respectively. The Naja h. venom had apoptotic effect against MCF-7 and Caco-2 cell lines through the elevation of p53 and depletion of Bcl-2 gene expression with increasing NO. and decreasing in GSH contents. The Leiurus q. venom had apoptotic effect against MCF-7 and Caco-2 cell lines through the elevation of Bax and depletion of Bcl-2 gene expression with elevation in NO. level. The Apis m. venom had apoptotic effect against MCF-7 and Caco-2 cell lines through the elevation of p53 and Bax with depletion of Bcl-2 gene expression and increasing NO. and decreasing in GSH contents. While 5-FU was toxic through depletion of Bcl-2 gene expression and increasing NO. level. Conclusion:- Finally, it can be concluded that snake (Naja h.), scorpion (Leiurus q.) and bee (Apis m.) venoms had anticancer potentials on human breast and colon cancer cells and this is positively related to the antioxidant profile and apoptotic gene expression.

  1. Abd-Elrahem, H. T.; El-Fiky, A. A.; Bakkar, A.; Mohamed, A. F. (2017): Honey Bee, Propolis and Bee Venom Derivatives Induced Apoptosis in Colorectal Cancer Cell Line HCT-116. Inventi Rapid: Mol. Pharmacol., 17(2):1-7.
  2. Adams, J. M. and Cory, S. (2007): The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene, 26(9): 1324-1337.
  3. Akbari, R. and Javar, H. A. (2013): Efficacy of Capecitabine and 5-Fluorouracil (5-FU) on the human breast cancer cell line (MCF7) – effect of concentration. J. Res. Commun., 1(16): 75-91.
  4. Al?Asmari, A. K.; Islam, M. and Al?Zahrani, A. M. (2016a): In vitro analysis of the anticancer properties of scorpion venom in colorectal and breast cancer cell lines.  Lett.,11(2): 1256-1262.
  5. Al-Asmari, A. K.; Riyasdeen, A.; Al-Shahrani, M. H. and Islam, M. (2016b): Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines. Targets. Ther.,9(16), 6485-6498.
  6. Al-Quraishy, S.; Dkhil, M. A. and Moneim, A. E. A. (2014): Hepatotoxicity and oxidative stress induced by Naja haje crude venom. Venom. Anim. Toxins Incl. Trop. Dis., 20(1): 42-52.
  7. Alyan, M. S.; Shalaby, M. A.; El-Sanousi, A. A.; Fahmy, A.; El-Sayed, M. and Shebl, R. I. (2014): Antiviral and Anticancer Potentials of Snake and Scorpion Venom Derivatives. Inventi Rapid: Mol. Pharmacol., 2014(2): 1-11.
  8. Ayman, M.; Mohmed, A. F.; Bakaar, A.; Shebl, R. l.; Sabatier, J. M. (2017): The Bacillus Calmette-Guérin Derived Purified Protein (PPD) Potentiates In-Vitro Anti-Cancer Activity of Cerastes cerastes Snake Venom in Colon and Prostate Cancer Cells. Inventi Rapid: Mol. Pharmacol., 17(1):1-10.
  9. Badr, G.; Al-Sadoon, M. K. and Rabah, D. M. (2013): Therapeutic efficacy and molecular mechanisms of snake (Walterinnesia aegyptia) venom-loaded silica nanoparticles in the treatment of breast cancer-and prostate cancer-bearing experimental mouse models. Free Radic. Biol. Med., 65(13): 175-189.
  10. Badr, G.; Sayed, D.; Maximous, D.; Mohamed, A. O. and Gul, M. (2014): Increased susceptibility to apoptosis and growth arrest of human breast cancer cells treated by a snake venom-loaded silica nanoparticles. Physiol. Biochem., 34(5): 1640-1651.
  11. Barrera, G.; Pizzimenti, S. and Dianzani, M. U. (2008): Lipid peroxidation: control of cell proliferation, cell differentiation and cell death. Aspects Med., 29(1): 1-8.
  12. Béchohra, L.; Laraba-Djebari, F. and Hammoudi-Triki, D. (2016): Cytotoxic activity of Androctonus australis hector venom and its toxic fractions on human lung cancer cell line.  Venom. Anim. Toxins Incl. Trop. Dis., 22(16): 14-29.
  13. Birben, E.; Sahiner, U. M.; Sackesen, C.; Erzurum, S. and Kalayci, O. (2012): Oxidative stress and antioxidant defense. World Allergy Organ. J., 5(1): 9-19.
  14. Bryan, J. (2009): From snake venom to ACE inhibitor-The discovery and rise of captopril. J., 282(7548): 455-459.
  15. Bunz, F.; Hwang, P. M.; Torrance, C.; Waldman, T.; Zhang, Y.; Dillehay, L.; Williams, J.; Lengauer, C.; Kinzler, K. W. and Vogelstein, B. (1999): Disruption of p53 in human cancer cells alters the responses to therapeutic agents.  Clin. Invest., 104(3): 263-269.
  16. Chan, J. Y.; Phoo, M. S.; Clement, M. V.; Pervaiz, S.; and Lee, S. C. (2008): Resveratrol displays converse dose-related effects on 5-fluorouracil-evoked colon cancer cell apoptosis: the roles of caspase-6 and p53. Cancer Boil. Ther., 7(8): 1305-1312.
  17. Corrêa, M. C.; Maria, D. A.; Moura-da-Silva, A. M.; Pizzocaro, K. F. and Ruiz, I. R. (2002): Inhibition of melanoma cells tumorigenicity by the snake venom toxin jararhagin. Toxicon, 40(6): 739-748.
  18. D’Suze, G.; Rosales, A.; Salazar, V. and Sevcik, C. (2010): Apoptogenic peptides from Tityus discrepans scorpion venom acting against the SKBR3 breast cancer cell line. Toxicon, 56(8): 1497-1505.
  19. Debin, J. A.; Maggio, J. E. and Strichartz, G. R. (1993): Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. J. Physiol. Cell Physiol., 264(2): C361-C369.
  20. Díaz-García, A.; Morier-Díaz, L.; Frión-Herrera, Y.; Rodríguez-Sánchez, H.; Caballero-Lorenzo, Y.; Mendoza-Llanes, D.; Riquenes-Garlobo, Y. and Fraga-Castro, J. A. (2013):In vitro anticancer effect of venom from Cuban scorpion Rhopalurus junceus against a panel of human cancer cell lines. Venom Res., 4(13): 5-12.
  21. Dimmeler, S.; Haendeler, J.; Nehls, M. and Zeiher, A. M. (1997): Suppression of apoptosis by nitric oxide via inhibition of interleukin-1?–converting enzyme (ice)-like and cysteine protease protein (cpp)-32–like proteases. Exp. Med., 185(4): 601-608.
  22. Dkhil, M. A.; Al-Quraishy, S.; Farrag, A. R. H.; Aref, A. M.; Othman, M. S. and Moneim, A. E. A. (2014): Oxidative stress and apoptosis are markers in renal toxicity following Egyptian cobra (Naja haje) envenomation. J. Zool., 46(6): 1719-1730.
  23. Draper, H. H. and Hadley, M. (1990): A review of recent studies on the metabolism of exogenous and endogenous malondialdehyde. Xenobiotica, 20(9): 901-907.
  24. Ebrahim, K.; Vatanpour, H.; Zare, A.; H Shirazi, F. and Nakhjavani, M. (2016): Anticancer Activity a of Caspian Cobra (Naja naja oxiana) snake Venom in Human Cancer Cell Lines Via Induction of Apoptosis.  J. Pharm. Res., 15, 101-112.?
  25. El Sharkawi, F. Z.; Saleh, S. S. and El Sayed, A. F. M. (2015): Potential anti cancer activity of snake venom, bee venom and their components in liver and breast carsenoma.  J. Pharm. Sci. Res., 6(8): 3224-3235.
  26. Ellman, G. L. (1959): Tissue sulfhydryl groups. Biochem. Biophys., 82(1): 70-77.
  27. Fatani, A. J.; Al-Zuhair, H. A.; Yaquob, H. I.; Abdel-Fattah, A. A.; El-Sayed, M. I. and El-Sayed, F. A. (2006): Protective effects of the antioxidant Ginkgo biloba extract and the protease inhibitor aprotinin against Leiurus quinquestriatus venom-induced tissue damage in rats. Venom. Anim. Toxins Incl. Trop. Dis., 12(2): 255-275.
  28. Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D. M.; Forman, D. and Bray, F. (2015): Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.  J. Cancer, 136(5): E359-E386.
  29. Fesik, S. W. (2005): Promoting apoptosis as a strategy for cancer drug discovery. Rev. Cancer, 5(11): 876-885.
  30. Franco, R., and Cidlowski, J. A. (2009): Apoptosis and glutathione: beyond an antioxidant. Cell Death Differ., 16(10): 1303-1314.
  31. Fulda, S. and Debatin, K. M. (2006): Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene, 25(34): 4798-4811.
  32. Gajski, G.; ?imbora-Zovko, T.; Rak, S.; Rožman, M.;Osmak, M. and Garaj?Vrhovac, V. (2014): Combined antitumor effects of bee venom and cisplatin on human cervical and laryngeal carcinoma cells and their drug resistant sublines. Appl.Toxicol., 34(12): 1332-1341.
  33. Gajski, G.; Domijan, A. M. and Garaj-Vrhovac, V. (2012): Alterations of GSH and MDA levels and their association with bee venom?induced DNA damage in human peripheral blood leukocytes. Mol. Mutagen., 53(6): 469-477.
  34. Gajski, G.; Domijan, A. M.; Žegura, B.; Štern, A.; Geri?, M.; Jovanovi?, I. N.; Jovanovi, I. N.; Vrhovac, I.; Maduni, J.; Breljak, D.; Filip, M. and Garaj-Vrhovac, V. (2016): Melittin induced cytogenetic damage, oxidative stress and changes in gene expression in human peripheral blood lymphocytes. Toxicon, 110(16): 56-67.
  35. Galvez, A.; Gimenez-Gallego, G.; Reuben, J. P.; Roy-Contancin, L.; Feigenbaum, P.; Kaczorowski, G. J. and Garcia, M. L. (1990): Purification and characterization of a unique, potent, peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus. Biol. Chem., 265(19): 11083-11090.
  36. Garcia-Calvo, M.; Leonard, R. J.; Novick, J.; Stevens, S. P.; Schmalhofer, W.; Kaczorowski, G. J. and Garcia, M. L. (1993): Purification, characterization, and biosynthesis of margatoxin, a component of Centruroides margaritatus venom that selectively inhibits voltage-dependent potassium channels. Biol. Chem., 268(25): 18866-18874.
  37. Giménez-Bonafé, P.; Tortosa, A. and Pérez-Tomás, R. (2009): Overcoming drug resistance by enhancing apoptosis of tumor cells. Cancer Drug Targets, 9(3): 320-340.
  38. Gomes, A.; Bhattacharjee, P.; Mishra, R.; Biswas, A. K.; Dasgupta, S. C. and Giri, B. (2010): Anticancer potential of animal venoms and toxins. Indian J. Exp. Biol., 48,(2): 93-103.
  39. Gomez-Monterrey, I.; Campiglia, P.; Scognamiglio, I.; Vanacore, D.; Dicitore, A.; Lombardi, A.; Caraglia, M.;Novellino, E. and Stiuso, P. (2013): DTNQ-Pro, a mimetic dipeptide, sensitizes human colon cancer cells to 5-fluorouracil treatment. Amino Acids, (13): 1-7.
  40. Goudet, C.; Chi, C. W. and Tytgat, J. (2002): An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch. Toxicon, 40(9): 1239-1258.
  41. Green, L. C.; Wagner, D. A.; Glogowski, J.; Skipper, P. L.; Wishnok, J. S. and Tannenbaum, S. R. (1982): Analysis of nitrate, nitrite, and [15 N] nitrate in biological fluids. Biochem., 126(1): 131-138.
  42. Gupta, S. D.; Gomes, A.; Debnath, A.; Saha, A. and Gomes, A. (2010): Apoptosis induction in human leukemic cells by a novel protein Bengalin, isolated from Indian black scorpion venom: through mitochondrial pathway and inhibition of heat shock proteins. Biol. Interact., 183(2): 293-303.
  43. Haddad, J. J. (2004): Redox and oxidant-mediated regulation of apoptosis signaling pathways: immuno-pharmaco-redox conception of oxidative siege versus cell death commitment. Immunopharmacol., 4(4): 475-493.
  44. Han, S. M.; Lee, K. G.; Yeo, J. H.; Kweon, H. Y.; Woo, S. O.; Lee, M. L.; Baek, H. J.; Kim, S. Y. and Park, K. K. (2007): Effect of honey bee venom on microglial cells nitric oxide and tumor necrosis factor-? production stimulated by LPS.  Ethnopharmacol., 111(1): 176-181.
  45. Hernández-Vargas, H.; Ballestar, E.; Carmona?Saez, P.; von Kobbe, C.; Bañón?Rodríguez, I.; Esteller, M.; Moreno-Bueno, G. and Palacios, J. (2006): Transcriptional profiling of MCF7 breast cancer cells in response to 5?Fluorouracil: Relationship with cell cycle changes and apoptosis, and identification of novel targets of p53. J. Cancer, 119(5): 1164-1175.
  46. Higuchi, Y. (2004): Glutathione depletion-induced chromosomal DNA fragmentation associated with apoptosis and necrosis. Cell. Mol. Med., 8(4): 455-464.
  47. Harvey, A. L. (2014): Toxins and drug discovery. Toxicon, 92, 193-200.
  48. Houghton, P.; Fang, R.; Techatanawat, I.; Steventon, G.; Hylands, P. J. and Lee, C. C. (2007): The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity. Methods, 42(4): 377-387.
  49. Ip, S. W.; Chu, Y. L.; Yu, C. S.; Chen, P. Y.; Ho, H. C.; Yang, J. S.; Huang, H. Y.; Chueh, F. S. and Chung, J. G. (2012): Bee venom induces apoptosis through intracellular Ca2+-modulated intrinsic death pathway in human bladder cancer cells. J. Urol., 19(1): 61-70.
  50. Ip, S. W.; Liao, S. S.; Lin, S. Y.; Lin, J. P.; Yang, J. S.; Lin, M. L.; Chen, G. W.; Lu, H. F.; Lin, M. W.; Han, S. M. and Chung, J. G. (2008a): The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells. In Vivo, 22(2): 237-245.
  51. Ip, S. W.; Wei, H. C.; Lin, J. P.; Kuo, H. M.; Liu, K. C.; Hsu, S. C.; Yang, J. S.; Mei-Dueyang; Chiu, T. H.; Han, S. M. and Chung, J. G. (2008b): Bee venom induced cell cycle arrest and apoptosis in human cervical epidermoid carcinoma Ca Ski cells. Anticancer Res.,28(2A): 833-842.
  52. Jain, K. K. (2014): Molecular biology of cancer in Applications of biotechnology in oncology. New York: Springer, pp. 1-22.
  53. Jang, M. H.; Shin, M. C.; Lim, S.; Han, S. M.; Park, H. J.; Shin, I.; Lee, J. S.; Kim, K. A.; Kim, E. H. and Kim, C. J. (2003): Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299.  Pharmacol. Sci., 91(2): 95-104.
  54. Jenkins, D. C.; Charles, I. G.; Thomsen, L. L.; Moss, D. W.; Holmes, L. S.; Baylis, S. A.; Rhodes, P.; Westmore, K.; Emson, P. C. and Moncada, S. (1995): Roles of nitric oxide in tumor growth. Natl. Acad. Sci., 92(10): 4392-4396.
  55. Jin, Y.; Heck, D. E.; DeGeorge, G.; Tian, Y. and Laskin, J. D. (1996): 5-Fluorouracil suppresses nitric oxide biosynthesis in colon carcinoma cells. Cancer Res., 56(9): 1978-1982.
  56. Jo, M.; Park, M. H.; Kollipara, P. S.; An, B. J.; Song, H. S.; Han, S. B.; Kim, J. H.; Song, M. J. and Hong, J. T. (2012): Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway.  Appl. Pharm., 258(1): 72-81.?
  57. Khalil, W. K.; Assaf, N.; ElShebiney, S. A. and Salem, N. A. (2015): Neuroprotective effects of bee venom acupuncture therapy against rotenone-induced oxidative stress and apoptosis. Int. 80(15): 79-86.
  58. Kim, C. M. (2013): Apitherapy–bee venom therapy. In Biotherapy-History, Principles and Practice. Springer, Netherlands, (pp. 77-112).
  59. Koçer, M. and Naz?ro?lu, M. (2013): Effects of 5-fluorouracil on oxidative stress and calcium levels in the blood of patients with newly diagnosed colorectal cancer.  Trace Elem. Res.,155(3): 327-332.
  60. Kruiswijk, F.; Labuschagne, C. F. and Vousden, K. H. (2015): p53 in survival, death and metabolic health: a lifeguard with a licence to kill.  Rev. Mol. cell Boil., 16(7): 393-405.
  61. Lee, H. L.; Park, M. H.; Son, D. J.; Song, H. S.; Kim, J. H.; Ko, S. C.; Song, M. J.; Lee, W. H.; Yoon, J. H.; Ham, Y. W.; Han, S. B. and Hong, J. H. (2015): Anti-cancer effect of snake venom toxin through down regulation of AP-1 mediated PRDX6 expression. Oncotarget,6(26): 22139-22151.
  62. Lipps, B. V. (1999): Novel snake venom proteins cytolytic to cancer cells in vitro and in vivoJ. Venom. Anim. Toxins, 5(2): 172-183.
  63. Lorenzo, L.; Chiara, P.; Antonio, C. and Calogero, F. (2012): Cancer pain management with venom of blue scorpion endemic in Cuba called Rhopalurus junceus “Escozul”. Open Cancer J., 5(8):1-2.
  64. Marnett, L. J. (1999): Lipid peroxidation—DNA damage by malondialdehyde. Res./Fund. Mol. Mech. Mut., 424(1): 83-95.
  65. Masters J. R. (3rd Ed.). (2000): Animal cell culture: a practical approach (pp. 3-10). New York: Oxford University Press.
  66. Moneim, A. E. A.; Ortiz, F.; Leonardo-Mendonca, R. C.; Vergano-Villodres, R.; Guerrero-Martínez, J. A.; López, L. C.; Acuna-Castroviejo, D. and Escames, G. (2015): Protective effects of melatonin against oxidative damage induced by Egyptian cobra (Naja haje) crude venom in rats. Acta Trop., 143(15): 58-65.
  67. Nicotera, P.; Bonfoco, E. and Brüne, B. (1995): Mechanisms for nitric oxide-induced cell death: involvement of apoptosis. Neuroimmunol., 5(4): 411-420.
  68. Nita, M. E.; Nagawa, H.; Tominaga, O.; Tsuno, N.; Fujii, S.; Sasaki, S.; Fu, C. G.; Takenoue, T.; Tsuruo, T. and Muto, T. (1998): 5-Fluorouracil induces apoptosis in human colon cancer cell lines with modulation of Bcl-2 family proteins. J. Cancer, 78(8): 986-992.
  69. Omran, M. A. A. (2003):In vitro anticancer effect of scorpion Leiurus quinquestriatus and Egyptian cobra venom on human breast and prostate cancer cell lines.  Med. Sci., 3: 66-86.
  70. Ortiz, E.; Gurrola, G. B.; Schwartz, E. F. and Possani, L. D. (2015): Scorpion venom components as potential candidates for drug development. Toxicon, 93(1):125-135.
  71. Park, M. H.; Choi, M. S.; Kwak, D. H.; Oh, K. W.; Yoon, D. Y.; Han, S. B.; Song, H. S.; Song, M. J. and Hong, J. T. (2011): Anti-cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF-?B. The Prostate,71(8): 801-812.?
  72. Prado, M.; Solano-Trejos, G. and Lomonte, B. (2010): Acute physiopathological effects of honeybee (Apis mellifera) envenoming by subcutaneous route in a mouse model. Toxicon, 56(6): 1007-1017.
  73. Shao, J.; Zhang, R.; Ge, X.; Yang, B. and Zhang, J. (2007): 45 Analgesic Peptides in Buthus martensii Karsch: A Traditional Chinese Animal Medicine. Asian J. Tradit. Med. 2 (2): 45-50.
  74. Simon, H. U.; Haj-Yehia, A. and Levi-Schaffer, F. (2000): Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis,5(5): 415-418.
  75. Son, D. J.; Park, M. H.; Chae, S. J.; Moon, S. O.; Lee, J. W.; Song, H. S.; Moon, D. C.; Kang, S. S.; Kwon, Y. E. and Hong, J. T. (2007): Inhibitory effect of snake venom toxin from Vipera lebetina turanica on hormone-refractory human prostate cancer cell growth: induction of apoptosis through inactivation of nuclear factor ?B. Cancer Therap., 6(2): 675-683.
  76. Song, J. K.; Jo, M. R.; Park, M. H.; Song, H. S.; An, B. J.; Song, M. J., Han, S. B. and Hong, J. T. (2012): Cell growth inhibition and induction of apoptosis by snake venom toxin in ovarian cancer cell via inactivation of nuclear factor ?B and signal transducer and activator of transcription 3. Pharm. Res., 35(5): 867-876.
  77. Suhail, N.; Bilal, N.; Khan, H. Y.; Hasan, S.; Sharma, S.; Khan, F.; Mansoor, T.; FICS and Banu, N. (2012): Effect of vitamins C and E on antioxidant status of breast cancer patients undergoing chemotherapy.  Clin. Pharm. Ther., 37(1): 22-26.
  78. Swaim, M. W.; Chiang, H. S. and Huang, T. F. (1996): Characterisation of platelet aggregation induced by PC-3 human prostate adenocarcinoma cells and inhibited by venom peptides, trigramin and rhodostomin. J. Cancer, 32(4): 715-721.
  79. Tu, W. C.; Wu, C. C.; Hsieh, H. L.; Chen, C. Y. and Hsu, S. L. (2008): Honeybee venom induces calcium-dependent but caspase-independent apoptotic cell death in human melanoma A2058 cells. Toxicon, 52(2): 318-329.
  80. Vyas, V. K.; Brahmbhatt, K.; Bhatt, H. and Parmar, U. (2013): Therapeutic potential of snake venom in cancer therapy: current perspectives. Asian Pac. J. Trop. Biomed., 3(2): 156-162.
  81. Yeh, C. H.; Peng, H. C.; Yang, R. S. and Huang, T. F. (2001): Rhodostomin, a snake venom disintegrin, inhibits angiogenesis elicited by basic fibroblast growth factor and suppresses tumor growth by a selective ?v?3 blockade of endothelial cells. Pharmacol., 59(5): 1333-1342.
  82. Yin, X. Y.; Jiang, J. M.; Liu, J. Y. and Zhu, J. R. (2007): Effects of endogenous nitric oxide induced by 5-fluorouracil and L-Arg on liver carcinoma in nude mice. World J. Gastroenterol., 13(46): 6249.
  83. Zargan, J.; Sajad, M.; Umar, S.; Naime, M.; Ali, S. and Khan, H. A. (2011a): Scorpion (Odontobuthus doriae) venom induces apoptosis and inhibits DNA synthesis in human neuroblastoma cells.  Cell. Biochem., 348(1): 173-181
  84. Zargan, J.; Sajad, M.; Umar, S.; Naime, M.; Ali, S. and Khan, H. A. (2011c): Scorpion (Androctonus crassicauda) venom limits growth of transformed cells (SH-SY5Y and MCF-7) by cytotoxicity and cell cycle arrest. Mol. Pathol., 91(1): 447-454.
  85. Zargan, J.; Umar, S.; Sajad, M.; Naime, M.; Ali, S. and Khan, H. A. (2011b): Scorpion venom (Odontobuthus doriae) induces apoptosis by depolarization of mitochondria and reduces S-phase population in human breast cancer cells (MCF-7).  In Vitro, 25(8): 1748-1756.
  86. Zhang, Y. Y.; Wu, L. C.; Wang, Z. P.; Wang, Z. X.; Jia, Q.; Jiang, G. S. and Zhang, W. D. (2009): Anti-proliferation effect of polypeptide extracted from scorpion venom on human prostate cancer cells in vitro. J. Clin. Med. Res., 1(1): 24-31.
  87. Zheng, J.; Lee, H. L.; Ham, Y. W.; Song, H. S.; Song, M. J. and Hong, J. T. (2015): Anti-cancer effect of bee venom on colon cancer cell growth by activation of death receptors and inhibition of nuclear factor kappa B. Oncotarget, 6(42): 44437.
  88. Zhou, J.; Qi, Y.; Diao, Q.; Wu, L.; Du, X.; Li, Y. and Sun, L. (2013): Cytotoxicity of melittin and apamin in human hepatic L02 and HepG2 cells in vitro. Toxin Rev., 32(4): 60-67.
  89. Zhou, Q.; Sherwin, R. P.; Parrish, C.; Richters, V.; Groshen, S. G.; Tsao-Wei, D. and Markland, F. S. (2000): Contortrostatin, a dimericdisintegrin from contortrix contortrix, inhibits breast cancer progression. Breast Cancer Res. Treat., 61(3): 249-259.

[Abdel-Aziz S. A. A, Mohamed A. F, Zahkouk S. A. M and Ali R. A. M. (2017); EVALUATION OF ANTICANCER ACTIVITY OF SOME VENOMOUS ANIMAL TOXINS ON HUMAN BREAST AND COLON CANCER CELL LINES AND RELATED ANTIOXIDANT PROFILE Int. J. of Adv. Res. 5 (Feb). 2036-2053] (ISSN 2320-5407). www.journalijar.com

Salma A. A. Abdel-Aziz
Faculty of girl for science and art, Ain Shams University, Naser City, Cairo, Egypt.

DOI:

Article DOI: 10.21474/IJAR01/3376      
DOI URL: https://dx.doi.org/10.21474/IJAR01/3376

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