Melittin: A lytic peptide with anticancer properties

Environmental Toxicology and Pharmacology

Volumn 36, Issue 2, 2013, Pages 697-705

  Gajski, Goran ^a   Garaj Vrhovac, Vera ^a  

^a INSTITUTE FOR MEDICAL RESEARCH AND OCCUPATIONAL HEALTH   (Croatia)

Author keywords

Anticancer effect; Apoptosis; Bee venom; Melittin; Necrosis; Tumour cells

Indexed keywords

BEE VENOM; CASPASE 3; CASPASE 9; GELATINASE B; INHIBITOR OF APOPTOSIS PROTEIN; MELITTIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PHORBOL 13 ACETATE 12 MYRISTATE; PROTEIN BAX; PROTEIN BCL 2; STAT3 PROTEIN; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND;

ADVERSE OUTCOME; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTHRITIS; BEE; CANCER CELL; CANCER INHIBITION; CELL CYCLE ARREST; CHRONIC INFLAMMATION; DOWN REGULATION; DRUG CYTOTOXICITY; DRUG DETERMINATION; DRUG EFFECT; DRUG MECHANISM; DRUG RESPONSE; DRUG STRUCTURE; HUMAN; IN VITRO STUDY; LIVER CELL CARCINOMA; METASTASIS; NONHUMAN; PAIN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; RHEUMATIC DISEASE; SIGNAL TRANSDUCTION; SKIN DISEASE; UPREGULATION;

ANTICANCER EFFECT; APOPTOSIS; BEE VENOM; MELITTIN; NECROSIS; TUMOUR CELLS;

ANIMALS; ANTINEOPLASTIC AGENTS; BEE VENOMS; CHEMISTRY, PHARMACEUTICAL; DRUG CARRIERS; HUMANS; MELITTEN; NANOPARTICLES;

EID: 84880996730     PISSN: 13826689     EISSN: 18727077     Source Type: Journal    
DOI: 10.1016/j.etap.2013.06.009     Document Type: Review

References (133)

1. Amin A.R., Kucuk O., Khuri F.R., Shin D.M. Perspectives for cancer prevention with natural compounds. J. Clin. Oncol. 2009, 27:2712-2725.
2. Baek Y.H., Huh J.E., Lee J.D., Choi do Y., Park D.S. Antinociceptive effect and the mechanism of bee venom acupuncture (Apipuncture) on inflammatory pain in the rat model of collagen-induced arthritis: Mediation by alpha2-Adrenoceptors. Brain Res. 2006, 1073-1074:305-310.
3. Bechinger B. Structure and functions of channel-forming peptides: magainins, cecropins, melittin and alamethicin. J. Membr. Biol. 1997, 156:197-211.
4. Bechinger B., Lohner K. Detergent-like actions of linear amphipathic cationic antimicrobial peptides. Biochim. Biophys. Acta 2006, 1758:1529-1539.
5. Binggeli R., Cameron I.L. Cellular potentials of normal and cancerous fibroblasts and hepatocytes. Cancer Res. 1980, 40:1830-1835.
6. Binggeli R., Weinstein R.C. Deficits in elevating membrane potential of rat fibrosarcoma cells after cell contact. Cancer Res. 1985, 45:235-241.
7. 1H NMR studies of self-aggregation of melittin in aqueous solution. Biochim. Biophys. Acta 1980, 622:231-244.
8. Borkow G., Chaim-Matyas A., Ovadia M. Binding of cytotoxin P4 from Naja nigricollis nigricollis to B16F10 melanoma and WEHI-3B leukemia cells. FEMS Microbiol. Immunol. 1992, 5:139-145.
9. Carrasquer G., Li M., Yang S., Schwartz M. Effect of melittin on PD, resistance and short-circuit current in the frog gastric mucosa. Biochim. Biophys. Acta 1998, 1369:346-354.
10. Chen Y.Q., Zhu Z.A., Hao Y.Q., Dai K.R., Zhang C. Effect of melittin on apoptosis and necrosis of U2 OS cells. Zhong Xi Yi Jie He Xue Bao 2004, 2:208-209.
11. Cherniak E.P. Bugs as drugs, Part 1: insects: the new alternative medicine for the 21st century?. Altern. Med. Rev. 2010, 15:124-135.
12. Das Gupta S., Debnath A., Saha A., Giri B., Tripathi G., Vedasiromoni J.R., Gomes A., Gomes A. Indian black scorpion (Heterometrus bengalensis Koch) venom induced antiproliferative and apoptogenic activity against human leukemic cell lines U937 and K562. Leuk. Res. 2007, 31:817-825.
13. Da Rocha A.B., Lopes R.M., Schwartsmann G. Natural products in anticancer therapy. Curr. Opin. Pharmacol. 2001, 1:364-369.
14. Debnath A., Chatterjee U., Das M., Vedasiromoni J.R., Gomes A. Venom of Indian monocellate cobra and Russell's viper show anticancer activity in experimental models. J. Ethnopharmacol. 2007, 111:681-684.
15. Dempsey C.E. The actions of melittin on membranes. Biochim. Biophys. Acta 1990, 1031:143-161.
16. Dotimas E.M., Hamid K.R., Hider R.C., Ragnarsson U. Isolation and structure analysis of bee venom mast cell degranulating peptide. Biochim. Biophys. Acta 1987, 911:285-293.
17. Duke R.C., Witter R.Z., Nash P.B., Young J.D., Ojcius D.M. Cytolysis mediated by ionophores and pore-forming agents: role of intracellular calcium in apoptosis. FASEB J. 1994, 8:237-246.
18. Eiseman J.L., von Bredow J., Alvares A.P. Effect of honeybee (Apis mellifera) venom on the course of adjuvant-induced arthritis and depression of drug metabolism in the rat. Biochem. Pharmacol. 1982, 31:1139-1146.
19. Feofanov A.V., Sharonov G.V., Astapova M.V., Rodionov D.I., Utkin Y.N., Arseniev A.S. Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal damage. Biochem. J. 2005, 390:11-18.
20. Findlay R.D., Taeusch H.W., David-Cu R., Walther F.J. Lysis of red blood cells and alveolar epithelial toxicity by therapeutic pulmonary surfactants. Pediatr. Res. 1995, 37:26-30.
21. Fletcher J.E., Jiang M.S. Possible mechanisms of action of cobra snake venom cardiotoxins and bee venom melittin. Toxicon 1993, 31:669-695.
22. Gajski G., Garaj-Vrhovac V. Genotoxic potential of bee venom (Apis Mellifera) on human peripheral blood lymphocytes in vitro using single cell gel electrophoresis assay. J. Environ. Sci. Health A: Toxic Hazard. Subst. Environ. Eng. 2008, 43:1279-1287.
23. Gajski G., Garaj-Vrhovac V. Radioprotective effects of honeybee venom (Apis Mellifera) against 915-MHz microwave radiation-induced DNA damage in Wistar rat lymphocytes. In vitro study. Int. J. Toxicol. 2009, 28:88-98.
24. Gajski G., Garaj-Vrhovac V. Increased frequency of sister chromatid exchanges and decrease in cell viability and proliferation kinetics in human peripheral blood lymphocytes after in vitro exposure to whole bee venom. J. Environ. Sci. Health A: Toxic Hazard. Subst. Environ. Eng. 2010, 45:1654-1659.
25. Gajski G., Čimbora-Zovko T., Osmak M., Garaj-Vrhovac V. Bee venom and melittin are cytotoxic against different types of tumor and non-tumor cell lines in vitro. Cancer Res. J. 2011, 4:159-174.
26. Gajski G., Garaj-Vrhovac V. Bee venom induced cytogenetic damage and decreased cell viability in human white blood cells after treatment in vitro: a multi-biomarker approach. Environ. Toxicol. Pharmacol. 2011, 32:201-211.
27. Gajski G., Domijan A.M., Garaj-Vrhovac V. Alterations of GSH and MDA levels and their association with bee venom-induced DNA damage in human peripheral blood leukocytes. Environ. Mol. Mutagen. 2012, 53:469-477.
28. Garaj-Vrhovac V., Gajski G. Evaluation of the cytogenetic status of human lymphocytes after exposure to a high concentration of bee venom in vitro. Arh. Hig. Rada Toksikol. 2009, 60:27-34.
29. Gao L., Yu S., Wu Y., Shan B. Effect of spider venom on cell apoptosis and necrosis rates in MCF-7 cells. DNA Cell Biol. 2007, 26:485-489.
30. Gevod V.S., Birdi K.S. Melittin and the 8-26 fragment. Differences in ionophoric properties as measured by monolayer method. Biophys. J. 1984, 45:1079-1083.
31. Giuliani A., Pirri G., Nicoletto S. Antimicrobial peptides: an overview of a promising class of therapeutics. Cent. Eur. J. Biol. 2007, 2:1-33.
32. Gomes A., Bhattacharjee P., Mishra R., Biswas A.K., Dasgupta S.C., Giri B., Debnath A., Gupta S.D., Das T., Gomes A. Anticancer potential of animal venoms and toxins. Indian J. Exp. Biol. 2010, 48:93-103.
33. Gotay C.C. Cancer prevention: major initiatives and looking into the future. Expert. Rev. Pharmacoecon. Outcomes Res. 2010, 10:143-154.
34. Graziose R., Lila M.A., Raskin I. Merging traditional Chinese medicine with modern drug discovery technologies to find novel drugs and functional foods. Curr. Drug. Discov. Technol. 2010, 7:2-12.
35. Guilford J.M., Pezzuto J.M. Natural products as inhibitors of carcinogenesis. Expert. Opin. Investig. Drugs 2008, 17:1341-1352.
36. Haase I., Czarnetzki B.M., Rosenbach T. Thrombin and melittin activate phospholipase C in human HaCaT keratinocytes. Exp. Dermatol. 1996, 5:84-88.
37. Habermann E. Bee and wasp venoms: the biochemistry and pharmacology of their peptides and enzymes are reviewed. Science 1972, 177:314-322.
38. Hait W.N., Grais L., Benz C., Cadman E.C. Inhibition of growth of leukemic cells by inhibitors of calmodulin: phenothiazines and melittin. Cancer Chemother. Pharmacol. 1985, 14:202-205.
39. Hait W.N., Lee G.L. Characteristics of the cytotoxic effects of the phenothiazine class of calmodulin antagonists. Biochem. Pharmacol. 1985, 34:3973-3978.
40. Harvey A. From demons to darlings: drugs from venoms. Drug Discov. Today 1998, 3:531-532.
41. Harvey A. Strategies for discovering drugs from previously unexplored natural products. Drug Discov. Today 2000, 5:294-300.
42. Havas L.J. Effect of bee venom on colchicine-induced tumours. Nature 1950, 166:567-568.
43. Hider R.C., Ragnarsson U. A proposal for the structure of apamin. FEBS Lett. 1980, 111:189-193.
44. Holle L., Song W., Holle E., Wei Y., Wagner T., Yu X. A matrix metalloproteinase 2 cleavable melittin/avidin conjugate specifically targets tumor cells in vitro and in vivo. Int. J. Oncol. 2003, 22:93-98.
45. Hoskin D.W., Ramamoorthy A. Studies on anticancer activities of antimicrobial peptides. Biochim. Biophys. Acta 2008, 1778:357-375.
46. Hu H., Chen D., Li Y., Zhang X. Effect of polypeptides in bee venom on growth inhibition and apoptosis induction of the human hepatoma cell line SMMC-7721 in-vitro and Balb/c nude mice in vivo. J. Pharm. Pharmacol. 2006, 58:83-89.
47. Hui S.W., Stewart C.M., Cherry R.J. Electron microscopic observation of the aggregation of membrane proteins in human erythrocyte by melittin. Biochim. Biophys. Acta 1990, 1023:335-340.
48. Hui L., Leung K., Chen H.M. The combined effects of antibacterial peptide cecropin A and anti-cancer agents on leukemia cells. Anticancer Res. 2002, 22:2811-2816.
49. 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., Chung J.G. The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells. In Vivo 2008, 22:237-245.
50. 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., Chung J.G. Bee venom induced cell cycle arrest and apoptosis in human cervical epidermoid carcinoma Ca Ski cells. Anticancer Res. 2008, 28:833-842.
51. Jang M.H., Shin M.C., Lim S., Han S.M., Park H.J., Shin I. Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299. J. Pharmacol. Sci. 2003, 91:95-104.
52. Jo M., Park M.H., Kollipara P.S., An B.J., Song H.S., Han S.B., Kim J.H., Song M.J., Hong J.T. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicol. Appl. Pharmacol. 2012, 258:72-81.
53. Kiesel L., Rabe T., Hauser G., Przylipiak A., Jadali F., Runnebaum B. Stimulation of luteinizing hormone release by melittin and phospholipase A2 in rat pituitary cells. Mol. Cell. Endocrinol. 1987, 51:1-6.
54. Killion J.J., Dunn J.D. Differential cytolysis of murine spleen, bone-marrow and leukemia cells by melittin reveals differences in membrane topography. Biochem. Biophys. Res. Commun. 1986, 139:222-227.
55. Knowles B.H., Farndale R.W. Activation of insect cell adenylate cyclase by Bacillus thuringiensis delta-endotoxins and melittin. Toxicity is independent of cyclic AMP. Biochem. J. 1988, 253:235-241.
56. Lad P.J., Shier W.T. Activation of microsomal guanylate cyclase by a cytotoxic polypeptide: melittin. Biochem. Biophys. Res. Commun. 1979, 89:315-321.
57. Ladokhin A.S., White S.H. Folding of amphipathic alpha-helices on membranes: energetics of helix formation by melittin. J. Mol. Biol. 1999, 285:1363-1369.
58. Lariviere W.R., Melzack R. The bee venom test: a new tonic-pain test. Pain 1996, 66:271-277.
59. Lauterwein J., Bösch C., Brown L.R., Wüthrich K. Physicochemical studies of the protein-lipid interactions in melittin-containing micelles. Biochim. Biophys. Acta 1979, 556:244-264.
60. 1H NMR studies of monomeric melittin in aqueous solution. Biochim. Biophys. Acta 1980, 622:219-230.
61. Lavialle F., Levin I.W., Mollay C. Interaction of melittin with dimyristoyl phosphatidylcholine liposomes: evidence for boundary lipid by Raman spectroscopy. Biochim. Biophys. Acta 1980, 600:62-71.
62. Lazo J.S., Hait W.N., Kennedy K.A., Braun I.D., Meandzija B. Enhanced bleomycin-induced DNA damage and cytotoxicity with calmodulin antagonists. Mol. Pharmacol. 1985, 27:387-393.
63. Lazo J.S., Chen D.L., Gallicchio V.S., Hait W.N. Increased lethality of calmodulin antagonists and bleomycin to human bone marrow and bleomycin-resistant malignant cells. Cancer Res. 1986, 46:2236-2240.
64. Lee G.L., Hait W.N. Inhibition of growth of C6 astrocytoma cells by inhibitors of calmodulin. Life Sci. 1985, 36:347-354.
65. Lee Y.J., Kang S.J., Kim B.M., Kim Y.J., Woo H.D., Chung H.W. Cytotoxicity of honeybee (Apis Mellifera) venom in normal human lymphocytes and HL-60 cells. Chem. Biol. Interact. 2007, 169:189-197.
66. Leuschner C., Hansel W. Membrane disrupting lytic peptides for cancer treatments. Curr. Pharm. Des. 2004, 10:2299-2310.
67. Lewis R.J., Garcia M.L. Therapeutic potential of venom peptides. Nat. Rev. Drug Discov. 2003, 2:790-802.
68. Li S.X., Ling C.Q., Liu X.Y. Impact of infection with recombinant adenovirus carrying melittin gene on CD54 expression in HepG2 cells. Di Yi Jun Yi Da Xue Xue Bao 2003, 23:300-305.
69. Li B., Ling C.Q., Zhang C., Gu W., Li S.X., Huang X.Q., Zhang Y.N., Yu C.Q. The induced apoptosis of recombinant adenovirus carrying melittin gene for hepatocellular carcinoma cell. Zhonghua Gan Zang Bing Za Zhi 2004, 12:453-455.
70. Li B., Gu W., Zhang C., Huang X.Q., Han K.Q., Ling C.Q. Growth arrest and apoptosis of the human hepatocellular carcinoma cell line BEL-7402 induced by melittin. Onkologie 2006, 29:367-371.
71. Ling C.Q., Li B., Zhang C., Gu W., Li S.X., Huang X.Q., Zhang Y.N. Anti-hepatocarcinoma effect of recombinant adenovirus carrying melittin gene. Zhonghua Gan Zang Bing Za Zhi 2004, 12:741-744.
72. Ling C.Q., Li B., Zhang C., Zhu D.Z., Huang X.Q., Gu W., Li S.X. Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma. Ann. Oncol. 2005, 16:109-115.
73. Liu X., Chen D., Xie L., Zhang R. Effect of honey bee venom on proliferation of K1735M2 mouse melanoma cells in vitro and growth of murine B16 melanomas in vivo. J. Pharm. Pharmacol. 2002, 54:1083-1089.
74. Liu S., Yu M., He Y., Xiao L., Wang F., Song C., Sun S., Ling C., Xu Z. Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway. Hepatology 2008, 47:1964-1973.
75. Mahady G.B., Liu C., Beecher C.W. Involvement of protein kinase and G proteins in the signal transduction of benzophenanthridine alkaloid biosynthesis. Phytochemistry 1998, 48:93-102.
76. Maher S., McClean S. Investigation of the cytotoxicity of eukaryotic and prokaryotic antimicrobial peptides in intestinal epithelial cells in vitro. Biochem. Pharmacol. 2006, 71:1289-1298.
77. Maher S., McClean S. Melittin exhibits necrotic cytotoxicity in gastrointestinal cells which is attenuated by cholesterol. Biochem. Pharmacol. 2008, 75:1104-1114.
78. Mau S.E., Vilhardt H. Cross talk between substance P and melittin-activated cellular signaling pathways in rat lactotroph-enriched cell cultures. J. Neurochem. 1997, 69:762-772.
79. McDonald J.A., Li F.P., Mehta C.R. Cancer mortality among beekeepers. J. Occup. Med. 1979, 21:811-813.
80. Mehta R.G., Pezzuto J.M. Discovery of cancer preventive agents from natural products: from plants to prevention. Curr. Oncol. Rep. 2002, 4:478-486.
81. Mehta R.G., Murillo G., Naithani R., Peng X. Cancer chemoprevention by natural products: how far have we come?. Pharm. Res. 2010, 27:950-961.
82. Meunier F.A., Frangez R., Benoit E., Ouanounou G., Rouzaire-Dubois B., Suput D., Molgó J. Ca(2+) and Na(+) contribute to the swelling of differentiated neuroblastoma cells induced by equinatoxin-II. Toxicon 2000, 38:1547-1560.
83. Moon D.O., Park S.Y., Heo M.S., Kim K.C., Park C., Ko W.S., Choi Y.H., Kim G.Y. Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt. Int. Immunopharmacol. 2006, 6:1796-1807.
84. Moon D.O., Park S.Y., Choi Y.H., Kim N.D., Lee C., Kim G.Y. Melittin induces Bcl-2 and caspase-3-dependent apoptosis through downregulation of Akt phosphorylation in human leukemic U937 cells. Toxicon 2008, 51:112-120.
85. Mufson R.A., Laskin J.D., Fisher P.B., Weinstein I.B. Melittin shares certain cellular effects with phorbol ester tumour promoters. Nature 1979, 280:72-74.
86. Nagaraju S., Mahadeswaraswamy Y.H., Girish K.S., Kemparaju K. Venom from spiders of the genus Hippasa: biochemical and pharmacological studies. Comp. Biochem. Physiol. C: Toxicol. Pharmacol. 2006, 144:1-9.
87. Nishioka D., Marcell V., Cunningham M., Khan M., Von Hoff D.D., Izbicka E. The use of early sea urchin embryos in anticancer drug testing. Methods Mol. Med. 2003, 85:265-276.
88. Nobili S., Lippi D., Witort E., Donnini M., Bausi L., Mini E., Capaccioli S. Natural compounds for cancer treatment and prevention. Pharmacol. Res. 2009, 59:365-378.
89. Oršolić N. Bee venom in cancer therapy. Cancer Metastasis Rev. 2012, 31:173-194.
90. Ownby C.L., Powell J.R., Jiang M.S., Fletcher J.E. Melittin and phospholipase A2 from bee (Apis Mellifera) venom cause necrosis of murine skeletal muscle in vivo. Toxicon 1997, 35:67-80.
91. Pan H., Soman N.R., Schlesinger P.H., Lanza G.M., Wickline S.A. Cytolytic peptide nanoparticles ('NanoBees') for cancer therapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2011, 3:318-327.
92. Papo N., Shai Y. Host defense peptides as new weapons in cancer treatment. Cell. Mol. Life Sci. 2005, 62:784-790.
93. Parekh H.S., Liu G., Wei M.Q. A new dawn for the use of traditional Chinese medicine in cancer therapy. Mol. Cancer 2009, 8:21.
94. Park J.H., Jeong Y.J., Park K.K., Cho H.J., Chung I.K., Min K.S., Kim M., Lee K.G., Yeo J.H., Park K.K., Chang Y.C. Melittin suppresses PMA-induced tumor cell invasion by inhibiting NF-kappaB and AP-1-dependent MMP-9 expression. Mol. Cell 2010, 29:209-215.
95. Park M.H., Choi M.S., Kwak D.H., Oh K.W., Yoon do Y., Han S.B., Song H.S., Song M.J., Hong J.T. Anti-cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF-κB. Prostate 2011, 71:801-812.
96. Pettit G.R., Hasler J.A., Paull K.D., Herald C.L. Antineoplastic agents. 76. The sea urchin Strongylocentrotus droebachiensis. J. Nat. Prod. 1981, 44:701-704.
97. Pratt J.P., Ravnic D.J., Huss H.T., Jiang X., Orozco B.S., Mentzer S.J. Melittin-induced membrane permeability: a nonosmotic mechanism of cell death. In Vitro Cell. Dev. Biol. Anim. 2005, 41:349-355.
98. Raghuraman H., Chattopadhyay A. Melittin: a membrane-active peptide with diverse functions. Biosci. Rep. 2007, 27:189-223.
99. Russell P.J., Hewish D., Carter T., Sterling-Levis K., Ow K., Hattarki M., Doughty L., Guthrie R., Shapira D., Molloy P.L., Werkmeister J.A., Kortt A.A. Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies. Cancer Immunol. Immunother. 2004, 53:411-421.
100. Schweitz H., Bidard J.N., Frelin C., Pauron D., Vijverberg H.P., Mahasneh D.M., Lazdunski M., Vilbois F., Tsugita A. Purification, sequence, and pharmacological properties of sea anemone toxins from Radianthus paumotensis. A new class of sea anemone toxins acting on the sodium channel. Biochemistry 1985, 24:3554-3561.
101. Saini S.S., Chopra A.K., Peterson J.W. Melittin activates endogenous phospholipase D during cytolysis of human monocytic leukemia cells. Toxicon 1999, 37:1605-1619.
102. 2-treated rat thymocytes by lipocortin I. Biochem. Biophys. Res. Commun. 1996, 220:643-647.
103. Shier W.T. Activation of high levels of endogenous phospholipase A2 in cultured cells. Proc. Natl. Acad. Sci. U.S.A. 1979, 76:195-199.
104. Shaposhnikova V.V., Egorova M.V., Kudryavtsev A.A., Levitman M.Kh., Korystov YuN. The effect of melittin on proliferation and death of thymocytes. FEBS Lett. 1997, 410:285-288.
105. Sharma S.V. Melittin resistance: a counterselection for ras transformation. Oncogene 1992, 7:193-201.
106. Sharma S.V. Melittin-induced hyperactivation of phospholipase A2 activity and calcium influx in ras-transformed cells. Oncogene 1993, 8:939-947.
107. Shipolini R.A. Biochemistry of bee venom. Handbook of Natural Toxins Vol. 2. Insect Poisons, Allergens, and Other Invertebrate Venoms 1984, 49-85. Marcel Dekker Inc., New York and Basel. T.A. Tu (Ed.).
108. Soletti R.C., de Faria G.P., Vernal J., Terenzi H., Anderluh G., Borges H.L., Moura-Neto V., Gabilan N.H. Potentiation of anticancer-drug cytotoxicity by sea anemone pore-forming proteins in human glioblastoma cells. Anticancer Drugs 2008, 19:517-525.
109. Song C.C., Lu X., Cheng B.B., Du J., Li B., Ling C.Q. Effects of melittin on growth and angiogenesis of human hepatocellular carcinoma BEL-7402 cell xenografts in nude mice. Ai Zheng 2007, 26:1315-1322.
110. Soman N.R., Baldwin S.L., Hu G., Marsh J.N., Lanza G.M., Heuser J.E., Arbeit J.M., Wickline S.A., Schlesinger P.H. Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth. J. Clin. Invest. 2009, 119:2830-2842.
111. Son D.J., Ha S.J., Song H.S., Lim Y., Yun Y.P., Lee J.W., Moon D.C., Park Y.H., Park B.S., Song M.J., Hong J.T. Melittin inhibits vascular smooth muscle cell proliferation through induction of apoptosis via suppression of nuclear factor-kappaB and Akt activation and enhancement of apoptotic protein expression. J. Pharmacol. Exp. Ther. 2006, 317:627-634.
112. Son D.J., Lee J.W., Lee Y.H., Song H.S., Lee C.K., Hong J.T. Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol. Ther. 2007, 115:246-270.
113. Soroceanu L., Gillespie Y., Khazaeli M.B., Sontheimer H. Use of chlorotoxin for targeting of primary brain tumors. Cancer Res. 1998, 58:4871-4879.
114. Stewart B.W., Kleihues P. World Cancer Report 2003, IARC Press, Lyon. second ed.
115. Stuhlmeier K.M. Apis Mellifera venom and melittin block neither NF-kappa B-p50-DNA interactions nor the activation of NF-kappa B, instead they activate the transcription of proinflammatory genes and the release of reactive oxygen intermediates. J. Immunol. 2007, 179:655-664.
116. Terra R.M., Guimarães J.A., Verli H. Structural and functional behavior of biologically active monomeric melittin. J. Mol. Graph. Model. 2007, 25:767-772.
117. Terwilliger T.C., Eisenberg D. The structure of melittin. I. Structure determination and partial refinement. J. Biol. Chem. 1982, 257:6010-6015.
118. Terwilliger T.C., Eisenberg D. The structure of melittin. II. Interpretation of the structure. J. Biol. Chem. 1982, 257:6016-6022.
119. Terwilliger T.C., Weissman L., Eisenberg D. The structure of melittin in the form I crystals and its implication for melittin's lytic and surface activities. Biophys. J. 1982, 37:353-361.
120. Tosteson M.T., Holmes S.J., Razin M., Tosteson D.C. Melittin lysis of red cells. J. Membr. Biol. 1985, 87:35-44.
121. Van Den Berg C.W., De Andrade R.M., Magnoli F.C., Marchbank K.J., Tambourgi D.V. Loxosceles spider venom induces metalloproteinase mediated cleavage of MCP/CD46 and MHCI and induces protection against C-mediated lysis. Immunology 2002, 107:102-110.
122. Varanda E.A., Monti R., Tavares D.C. Inhibitory effect of propolis and bee venom on the mutagenicity of some direct- and indirect-acting mutagens. Teratog. Carcinog. Mutagen. 1999, 19:403-413.
123. Vogel H. Incorporation of melittin into phosphatidylcholine bilayers. Study of binding and conformational changes. FEBS Lett. 1981, 134:37-42.
124. Wang W.X., Ji Y.H. Scorpion venom induces glioma cell apoptosis in vivo and inhibits glioma tumor growth in vitro. J. Neurooncol. 2005, 73:1-7.
125. Wang C., Chen T., Zhang N., Yang M., Li B., Lü X., Cao X., Ling C. Melittin, a major component of bee venom, sensitizes human hepatocellular carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by activating CaMKII-TAK1-JNK/p38 and inhibiting IkappaBalpha kinase-NFkappaB. J. Biol. Chem. 2009, 284:3804-3813.
126. Watala C., Gwoździński K. Melittin-induced alterations in dynamic properties of human red blood cell membranes. Chem. Biol. Interact. 1992, 82:135-149.
127. Watala C., Kowalczyk J.K. Hemolytic potency and phospholipase activity of some bee and wasp venoms. Comp. Biochem. Physiol. C 1990, 97:187-194.
128. Weston K.M., Raison R.L. Interaction of melittin with a human lymphoblastoid cell line, HMy2. J. Cell. Biochem. 1998, 68:164-173.
129. Yang R.S., Tang C.H., Chuang W.J., Huang T.H., Peng H.C., Huang T.F., Fu W.M. Inhibition of tumor formation by snake venom disintegrin. Toxicon 2005, 45:661-669.
130. Yang Z.L., Ke Y.Q., Xu R.X., Peng P. Melittin inhibits proliferation and induces apoptosis of malignant human glioma cells. Nan Fang Yi Ke Da Xue Xue Bao 2007, 27:1775-1777.
131. Zhang C., Li B., Lu S.Q., Li Y., Su Y.H., Ling C.Q. Effects of melittin on expressions of mitochondria membrane protein 7A6, cell apoptosis-related gene products Fas and Fas ligand in hepatocarcinoma cells. Zhong Xi Yi Jie He Xue Bao 2007, 5:559-563.
132. Zhao Y.H., Bai Y., Cui H., Liao F.P., Gao X.Y. Design and expression in Pichia pastoris of melittin and research of antibacterial activity increasing of melittin. Life. Sci. Res. 2006, 10:313-319.
133. Zhu H.G., Tayeh I., Israel L., Castagna M. Different susceptibility of lung cell lines to inhibitors of tumor promotion and inducers of differentiation. J. Biol. Regul. Homeost. Agents 1991, 5:52-58.