Top

Published in:

01-06-2012 | NON-THEMATIC REVIEW

Bee venom in cancer therapy

Author: Nada Oršolić

Published in: Cancer and Metastasis Reviews | Issue 1-2/2012

Abstract

Bee venom (BV) (api-toxin) has been widely used in the treatment of some immune-related diseases, as well as in recent times in treatment of tumors. Several cancer cells, including renal, lung, liver, prostate, bladder, and mammary cancer cells as well as leukemia cells, can be targets of bee venom peptides such as melittin and phospholipase A2. The cell cytotoxic effects through the activation of PLA2 by melittin have been suggested to be the critical mechanism for the anti-cancer activity of BV. The induction of apoptotic cell death through several cancer cell death mechanisms, including the activation of caspase and matrix metalloproteinases, is important for the melittin-induced anti-cancer effects. The conjugation of cell lytic peptide (melittin) with hormone receptors and gene therapy carrying melittin can be useful as a novel targeted therapy for some types of cancer, such as prostate and breast cancer. This review summarizes the current knowledge regarding potential of bee venom and its compounds such as melittin to induce cytotoxic, antitumor, immunomodulatory, and apoptotic effects in different tumor cells in vivo or in vitro. The recent applications of melittin in various cancers and a molecular explanation for the antiproliferative properties of bee venom are discussed.

Habermann, E. (1972). Bee and wasp venoms. The biochemistry and pharmacology of their peptides and enzymes are reviewed. Science, 177, 314–322.PubMedCrossRef

Raghuraman, H., & Chattopadhyay, A. (2007). Melittin: a membrane-active peptide with diverse functions. Bioscience Reports, 27(4–5), 189S–223S.CrossRef

Kwon, Y. B., Lee, J. D., Lee, H. J., Han, H. J., Mar, W. C., Kang, S. K., Beitz, A. J., & Lee, J. H. (2001). Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses. Pain, 90, 271–280.PubMedCrossRef

Park, H. J., Lee, S. H., Son, D. J., Oh, K. W., Kim, K. H., Song, H. S., Kim, G. J., Oh, G. T., Yoon, D. Y., & Hong, J. T. (2004). Antiarthritic effect of bee venom: inhibition of inflammation mediator generation by suppression of NF-kappaB through interaction with the p50 subunit. Arthritis and Rheumatism, 50(11), 3504–3515.PubMedCrossRef

Liu, X., Chen, D., Xie, L., & Zhang, R. (2002). 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, 54(8), 1083–1089.PubMedCrossRef

Oršolić, N., Knežević, A., Šver, L., Terzić, S., Hackenberger, B. K., & Bašić, I. (2003). Influence of honey bee products on transplantable murine tumors. Veterinary and Comparative Oncology, 1(4), 216–226.PubMedCrossRef

Oršolić, N., Šver, L., Verstovšek, S., Terzić, S., & Bašić, I. (2003). Inhibition of mammary carcinoma cell proliferation in vitro and tumor growth in vivo by bee venom. Toxicon, 41(7), 861–870.PubMedCrossRef

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. (2004). Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies. Cancer Immunology, Immunotherapy, 53(5), 411–421.PubMedCrossRef

Moon, D. O., Park, S. Y., Heo, M. S., Kim, K. C., Park, C., & Ko, W. S. (2006). Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt. International Immunopharmacology, 6(12), 1796–1807.PubMedCrossRef

10.

Varanda, E. A., & Tavares, D. C. (1998). Radioprotection: mechanism and radioprotective agents including honey bee venom. Venom Anim Toxins, 4(1), 5–21.

11.

Varanda, E. A., Monti, R., & Tavares, D. C. (1999). Inhibitory effect of propolis and bee venom on the mutagenicity of some direct- and indirect-acting mutagens. Teratogenesis Carcinogenesis and Mutagenesis, 19(6), 403–413.CrossRef

12.

Nam, K. W., Je, K. H., Lee, J. H., Han, H. J., Lee, H. J., Kang, S. K., & Mar, W. (2003). Inhibition of COX-2 activity and proinflammatory cytokines (TNF-alpha and IL-1beta) production by water-soluble sub-fractionated parts from bee (Apis mellifera) venom. Archives of Pharmacal Research, 26(5), 383–388.PubMedCrossRef

13.

Kim, H. W., Kwon, Y. B., Ham, T. W., Roh, D. H., Yoon, S. Y., Lee, H. J., Han, H. J., Yang, I. S., Beitz, A. J., & Lee, J. H. (2003). Acupoint stimulation using bee venom attenuates formalin-induced pain behavior and spinal cord fos expression in rats. Journal of Veterinary and Medicine Science, 65(3), 349–355.CrossRef

14.

Son, D. J., Lee, J. W., Lee, Y. H., Song, H. S., Lee, C. K., & Hong, J. T. (2007). Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacology & Therapeutics, 115(2), 246–270.CrossRef

15.

Jang, M. H., Shin, M. C., Lim, S., Han, S. M., Park, H. J., & Shin, I. (2003). Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299. Jounal of Pharmacology Science, 91(2), 95–104.CrossRef

16.

Yin, C. S., Lee, H. J., Hong, S. J., Chung, J. H., & Koh, H. G. (2005). Microarray analysis of gene expression in chondrosarcoma cells treated with bee venom. Toxicon, 45(1), 81–91.PubMedCrossRef

17.

Hu, H., Chen, D., Li, Y., & Zhang, X. (2006). 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. Journal of Pharmacy and Pharmacology, 58(1), 83–89.PubMedCrossRef

18.

Han, S., Lee, K., Yeo, J., Kweon, H., Woo, S., Lee, M., Baek, H., Kim, S., & Park, K. (2007). Effect of honey bee venom on microglial cells nitric oxide and tumor necrosis factor-alpha production stimulated by LPS. Journal of Ethnopharmacology, 111(1), 176–181.PubMedCrossRef

19.

Hong, S. J., Rim, G. S., Yang, H. I., Yin, C. S., Koh, H. G., Jang, M. H., Kim, C. J., Choe, B. K., & Chung, J. H. (2005). Bee venom induces apoptosis through caspase-3 activation in synovial fibroblasts of patients with rheumatoid arthritis. Toxicon, 46, 39–45.PubMedCrossRef

20.

Yusuf, N., Irby, C., Katiyar, S. K., & Elmets, C. A. (2007). Photoprotective effects of green tea polyphenols. Photodermatology, Photoimmunology and Photomedicine, 23, 48–56.PubMedCrossRef

21.

Leuschner, C., & Hansel, W. (2004). Membrane disrupting lytic peptides for cancer treatments. Current Pharmaceutical Desing, 10, 2299–2310.CrossRef

22.

Ling, C. Q., Li, B., Zhang, C., Gu, W., Li, S. X., Huang, X. Q., & Zhang, Y. N. (2004). Anti-hepatocarcinoma effect of recombinant adenovirus carrying melittin gene. Zhonghua Gan Zang Bing Za Zhi, 12(12), 741–744.PubMed

23.

Eisenberg, D. (1984). Three-dimensional structure of membrane and surface proteins. Annual Review of Biochemistry, 53, 595–623.PubMedCrossRef

24.

Wade, D., Boman, A., Wahlin, B., Drain, C. M., Andreu, D., Boman, H. G., & Merrifield, R. B. (1990). The Proceedings of the National Academy of Sciences USA, 87, 4761–4765.CrossRef

25.

Katsu, T., Kuroko, M., Morikawa, T., Sanchika, K., Fujita, Y., Yamamura, H., & Uda, M. (1989). Mechanism of membrane damage induced by the amphipathic peptides gramicidin S and melittin. Biochimica et Biophysica Acta, 983, 135–141.PubMedCrossRef

26.

Dempsey, C. E. (1990). The actions of melittin on membranes. Biochimica et Biophysica Acta, 1031, 143–161.PubMed

27.

Ladokhin, A. S., Selsted, M. E., & White, S. H. (1997). Sizing membrane pores in lipid vesicles by leakage of co-encapsulated markers: pore formation by melittin. Biophysical Journal, 72, 1762–1766.PubMedCrossRef

28.

Kiesel, L., Rabe, T., Hauser, G., Przylipiak, A., Jadali, F., & Runnebaum, B. (1987). Stimulation of luteinizing hormone release by melittin and phospholipase A2 in rat pituitary cells. Molecular and Cellular Endocrinology, 51, 1–6.PubMedCrossRef

29.

Hui, S. W., Stewart, C. M., & Cherry, R. J. (1990). Biochimica et Biophysica Acta, 1023, 335–340.PubMedCrossRef

30.

Carrasquer, G., Li, M., Yang, S., & Schwartz, M. (1998). Effect of melittin on PD, resistance and short-circuit current in the frog gastric mucosa. Biochimica et Biophysica Acta, 1369, 346–354.PubMedCrossRef

31.

Mahady, G. B., Liu, C., & Beecher, C. W. (1998). Involvement of protein kinase and G proteins in the signal transduction of benzophenanthridine alkaloid biosynthesis. Phytochemistry, 48, 93–102.PubMedCrossRef

32.

Mau, S. E., & Vilhardt, H. (1997). Cross talk between substance P and melittin-activated cellular signaling pathways in rat lactotroph-enriched cell cultures. Journal of Neurochemistry, 69, 762–772.PubMedCrossRef

33.

Knowles, B., & Farndale, R. W. (1988). Activation of insect cell adenylate cyclase by Bacillus thuringiensis delta-endotoxins and melittin. Toxicity is independent of cyclic AMP. Biochemistry Journal, 253, 235–241.

34.

Haber, M. T., Fukui, T., Lebowitz, M. S., & Lowenstein, J. M. (1991). Activation of phosphoinositide-specific phospholipase C delta from rat liver by polyamines and basic proteins. Archives of Biochemistra and Biophysics, 288, 243–249.CrossRef

35.

Haase, I., Czarnetzki, B. M., & Rosenbach, T. (1996). Thrombin and melittin activate phospholipase C in human HaCaT keratinocytes. Experimental Dermatology, 5, 84–88.PubMedCrossRef

36.

Lee, S. Y., Yeo, E., & Choi, M.-U. (1998). Phospholipase D activity in L1210 cells: a model for oleate-activated phospholipase D in intact mammalian cells. Biochemistry and Biophysics Reserch Communication, 244, 825–831.CrossRef

37.

Liu, S.-Y., Tappia, P. S., Dai, J., Williams, S. A., & Panagia, V. (1998). Phospholipase A2-mediated activation of phospholipase D in rat heart sarcolemma. Journal of Molecular and Cellular Cardiology, 30, 1203–1214.PubMedCrossRef

38.

Saini, S. S., Chopra, A. K., & Peterson, J. W. (1999). Melittin activates endogenous phospholipase D during cytolysis of human monocytic leukemia cells. Toxicon, 37, 1605–1619.PubMedCrossRef

39.

Fukushima, N., Kohno, M., Kato, T., Kawamoto, S., Okuda, K., Misu, Y., & Ueda, H. (1998). Melittin, a metabostatic peptide inhibiting Gs activity. Peptides, 19(5), 811–819.PubMedCrossRef

40.

Dennis, E. A. (1994). Diversity of group types, regulation, and function of phospholipase A2. Journal of Biological Chemistry, 269, 13057–13060.PubMed

41.

Six, D. A., & Dennis, E. A. (2000). The expanding superfamily of phospholipase A(2) enzymes: classification and characterization. Biochimica et Biophysica Acta, 1488, 1–19.PubMed

42.

Valentin, E., & Lambeau, G. (2000). What can venom phospholipases A(2) tell us about the functional diversity of mammalian secreted phospholipases A(2)? Biochimie, 82, 815–831.PubMedCrossRef

43.

Kudo, I., & Murakami, M. (2002). Phospholipase A2 enzymes. Prostaglandins & Other Lipid Mediators, 68–69, 3–58.CrossRef

44.

Lambeau, G., Schmid-Alliana, A., Lazdunski, M., & Barhanin, J. (1990). Identification and purification of a very high affinity binding protein for toxic phospholipases A2 in skeletal muscle. Journal of Biology and Chemistry, 265, 9526–9532.

45.

Lambeau, G., & Lazdunski, M. (1999). Receptors for a growing family of secreted phospholipases A2. Trends in Pharmacology Science, 20, 162–170.CrossRef

46.

Fonteh, A. N., Atsumi, G., LaPorte, T., & Chiltonm, F. H. (2000). Secretory phospholipase A2 receptor-mediated activation of cytosolic phospholipase A2 in murine bone marrow-derived mast cells. Journal of Immunology, 165, 2773–2782.

47.

Graler, M. H., & Goetzl, E. J. (2002). Lysophospholipids and their G protein-coupled receptors in inflammation and immunity. Biochimica et Biophysica Acta, 1582, 168–174.PubMed

48.

Kabarowski, J. H., Xu, Y., & Witte, O. N. (2002). Lysophosphatidyl choline as a ligand for immunoregulation. Biochemistry and Pharmacology, 64, 161–167.CrossRef

49.

Andresen, T. L., Jensen, S. S., Madsen, R., & Jorgensen, K. (2005). Synthesis and biological activity of anticancer ether lipids that are specifically released by phospholipase A2 in tumor tissue. Journal of Medicinal Chemistry, 48, 7305–7314.PubMedCrossRef

50.

Ruiter, G. A., Verheij, M., Zerp, S. F., & van Blitterswijk, W. J. (2001). Alkyl-lysophospholipids as anticancer agents and enhancers of radiation-induced apoptosis. International Journal of Radiation Oncology, Biology, Physics, 49, 415–419.PubMedCrossRef

51.

Ruiter, G. A., Zerp, S. F., Bartelink, H., van Blitterswijk, W. J., & Verheij, M. (2003). Anti-cancer alkyl-lysophospholipids inhibit the phosphatidylinositol 3-kinase-Akt/PKB survival pathway. Anti-Cancer Drugs, 14, 167–173.PubMedCrossRef

52.

Samadder, P., Bittman, R., Byun, H. S., & Arthur, G. (2004). Synthesis and use of novel ether phospholipid enantiomers to probe the molecular basis of the antitumor effects of alkyllysophospholipids: correlation of diferential activation of c-Jun NH(2)-terminal protein kinase with antiproliferative effects in neuronal tumor cells. Journal of Medicinal Chemistry, 47, 2710–2713.PubMedCrossRef

53.

Winder, D., Günzburg, W. H., Erfle, V., & Salmons, B. (1998). Expression of antimicrobial peptides has an antitumour effect in human cells. Biochemical and Biophysical Resech Commununication, 242(3), 608–612.CrossRef

54.

Oršolić, N., Terzić, S., Šver, L., & Bašić, I. (2005). Honey-bee products in preventive and/or therapy of murine transplantable tumours. Journal of the Science of Food and Agriculture, 85, 363–370.CrossRef

55.

Duke, R. C., Witter, R. Z., Nash, P. B., Young, J. D., & Ojcius, D. M. (1994). Cytolysis mediated by ionophores and pore-forming agents: role of intracellular calcium in apoptosis. The FASEB Journal, 8, 237–246.

56.

Li, B., Gu, W., Zhang, C., Huang, X. Q., Han, K. Q., & Ling, C. Q. (2006). Growth arrest and apoptosis of the human hepatocellular carcinoma cell line BEL-7402 induced by melittin. Onkologie, 29(8–9), 367–371.PubMedCrossRef

57.

Chu, S. T., Cheng, H. H., Huang, C. J., Chang, H. C., Chi, C. C., Su, H. H., Hsu, S. S., Wang, J. L., Chen, I. S., Liu, S. I., Lu, Y. C., Huang, J. K., Ho, C. M., & Jan, C. R. (2007). Phospholipase A2-independent Ca2+ entry and subsequent apoptosis induced by melittin in human MG63 osteosarcoma cells. Life Science, 80(4), 364–369.CrossRef

58.

Zhang, C., Li, B., Lu, S. Q., Li, Y., Su, Y. H., & Ling, C. Q. (2007). 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, 5, 559–563.PubMedCrossRef

59.

Liu, S., Yu, M., He, Y., Xiao, L., Wang, F., Song, C., Sun, S., Ling, C., & Xu, Z. (2008). Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway. Hepatology, 47(6), 1964–1973.PubMedCrossRef

60.

Sharma, S. V. (1993). Melittin-induced hyperactivation of phospholipase A2 activity and calcium influx in ras-transformed cells. Oncogene, 8(4), 939–947.PubMed

61.

Sharma, S. V. (1992). Melittin resistance: a counterselection for ras transformation. Oncogene, 7, 193–201.PubMed

62.

Oršolić, N. (2009). Potentiation of Bleomycin lethality on HeLa and V79 cells by bee venom. Arhives of Industrial Hygiene and Toxicology, 60, 317–326.CrossRef

63.

Tsuro, T., Iida, H., Tsukagoshi, S., & Sakurai, Y. (1982). Increased accumulation of vineristine and adriamycin in drug-resistant P388 tumor cells following with calcium antagonists and calmodulin inhibitors. Cancer Reserch, 42, 4730–4733.

64.

Chafouleas, J. G., Botton, W. E., & Means, A. R. (1984). Potentiation of bleomycin lethality by anti-calmodulin drugs: a role for calmodulin in DNA repair. Science, 224, 1346–1348.PubMedCrossRef

65.

Lee, G. L., & Hait, W. N. (1985). Growth inhibition of C6 astrocytoma cells by inhibitions of calmodulin. Life Science, 36, 347–354.CrossRef

66.

Lazo, J. S., Hait, W. N., Kennedy, K. A., Braun, I. D., & Meandzija, B. (1985). Enhanced bleomycin-induced DNA damage and cytotoxicity with calmodulin antagonists. Molecular Pharmacology, 27(3), 387–393.PubMed

67.

Killion, J. J., & Dunn, J. D. (1986). Differential cytolysis of murine spleen, bone-marrow and leukemia cells by melittin reveals differences in membrane topography. Biochemical and Biophysical Research Communication, 139, 222–227.CrossRef

68.

Chueng, W. Y. (1982). Calmodulin: an overview. Federation Proceedings, 41(7), 2253–2257.

69.

Gerst, J. E., & Salomon, Y. (1987). Inhibition by melittin and fluphenazine of melanotropin receptor function and adenylate cyclase in M2R melanoma cell membranes. Endocrinology, 121(5), 1766–1772.PubMedCrossRef

70.

Vento, R., D'Alessandro, N., Giuliano, M., Lauricella, M., Carabillò, M., & Tesoriere, G. (2000). Induction of apoptosis by arachidonic acid in human retinoblastoma Y79 cells: involvement of oxidative stress. Experimental Eye Reserch, 70(4), 503–517.CrossRef

71.

Arioka, M., Cheon, S. H., Ikeno, Y., Nakashima, S., & Kitamoto, K. (2005). A novel neurotrophic role of secretory phospholipases A2 for cerebellar granule neurons. FEBS Letters, 579(12), 2693–2701.PubMedCrossRef

72.

Shaposhnikova, V. V., Egorova, M. V., Kudryavtsev, A. A., Levitman, M. Kh., & Korystov, Yu. N. (1997). The effect of melittin on proliferation and death of thymocytes. FEBS Letters, 410(2–3), 285–288.PubMedCrossRef

73.

Oršolić, N., Šver, L., Bendelja, K., & Bašić, I. (2001). Antitumor activity of bee venom. Periodicum Biologorum, 103, 49–54.

74.

Weston, K. M., & Raison, R. L. (1998). Interaction of melittin with a human lymphoblastoid cell line, HMy2. Journal Cell Biochemistry, 68(2), 164–173.CrossRef

75.

Tosteson, M. T., & Tosteson, D. C. (1981). The sting: melittin forms channels in lipid bilayers. Biophysics Journal, 36, 109–116.CrossRef

76.

Vogel, H., & Jähnig, F. (1986). The structure of melittin in membranes. Biophysical Journal, 50(4), 573–582.PubMedCrossRef

77.

Laine, R. O., Morgan, B. P., & Esser, A. F. (1988). Comparison between complement and melittin hemolysis: anti-melittin antibodies inhibit complement lysis. Biochemistry, 27(14), 5308–5314.PubMedCrossRef

78.

Pawlak Pawlak, M., Meseth, U., Dhanapal, B., Mutter, M., & Vogel, H. (1994). Template-assembled melittin: structural and functional characterization of a designed, synthetic channel-forming protein. Protein Science, 3(10), 1788–1805.CrossRef

79.

Benachir, T., & Lafleur, M. (1995). Study of vesicle leakage induced by melittin. Biochimica et Biophysica Acta, 1235(2), 452–460.PubMedCrossRef

80.

DeGrado, W. F., Musso, G. F., Lieber, M., Kaiser, E. T., & Kézdy, F. J. (1982). Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue. Biophysical Journal, 37(1), 329–338.PubMedCrossRef

81.

Matsuzaki, K., Yoneyama, S., & Miyajima, K. (1997). Pore formation and translocation of melittin. Biophysical Journal, 73(2), 831–838.PubMedCrossRef

82.

Shier, W. T. (1979). Activation of high levels of endogenous phospholipase A2 in cultured cells. The Proceedings of the National Academy of Sciences USA, 76(1), 195–199.CrossRef

83.

Fletcher, J. E., & Jiang, M. S. (1993). Possible mechanisms of action of cobra snake venom cardiotoxins and bee venom melittin. Toxicon, 31(6), 669–695.PubMedCrossRef

84.

Sarin, A., Adams, D. H., & Henkart, P. A. (1993). Protease inhibitors selectively block T cell receptor-triggered programmed cell death in a murine T cell hybridoma and activated peripheral T cells. The Journal of Experimental Medicine, 178(5), 1693–1700.PubMedCrossRef

85.

Squìer, M. K., Miller, A. C., Malkinson, A. M., & Cohen, J. J. (1994). Calpain activation in apoptosis. Journal of Cell Physiology, 159(2), 229–237.CrossRef

86.

Goodman, S. R., Krebs, K. E., Whitfield, C. F., Riederer, B. M., & Zagon, I. S. (1988). Spectrin and related molecules. CRC Critical Reviews in Biochemistry, 23(2), 171–234.PubMedCrossRef

87.

Fox, J. E. B., Reynolds, C. C., Morrow, J. S., & Phillips, D. R. (1987). Spectrin is associated with membrane-bound actin filaments in platelets and is hydrolyzed by the Ca²⁺-dependent protease during platelet activation. Blood, 69, 537–545.PubMed

88.

Harris, A. S., Croall, D. E., & Morrow, J. S. (1988). The calmodulin-binding site in alpha-fodrin is near the calcium-dependent protease-I cleavage site. Journal of Biological Chemistry, 263, 15754–15761.PubMed

89.

Harris, A. S., & Morrow, J. S. (1990). Calmodulin and calcium-dependent protease I coordinately regulate the interaction of fodrin with actin. The Proceedings of the National Academy of Sciences USA, 87, 3009–3013.CrossRef

90.

Arora, A.S., deGroen, P., Emori, Y., Gores, G.J. (1996) A cascade of degradative hydrolase activity contributes to hepatocyte necrosis during anoxia. The American Journal of Physiology, 270(2 Pt1), G238–G245.

91.

Wu, Y. L., Jiang, X. R., Newland, A. C., & Kelsey, S. M. (1998). Failure to activate cytosolic phospholipase A2 causes TNF resistance in human leukemic cells. Journal of Immunology, 160(12), 5929–5935.

92.

Midoux, P., Mayer, R., & Monsigny, M. (1995). Membrane permeabilization by alpha-helical peptides: a flow cytometry study. Biochimica et Biophysica Acta, 1239, 249–256.PubMedCrossRef

93.

Clapp, L. E., Klette, K. L., DeCoster, M. A., Bernton, E., Petras, J. M., Dave, J. R., Laskosky, M. S., Smallridge, R. C., & Tortella, F. C. (1995). Phospholipase A2-induced neurotoxicity in vitro and in vivo in rats. Brain Reserch, 693, 101–111.CrossRef

94.

Lee, S. Y., Park, H. S., Lee, S. J., & Choi, M. U. (2001). Melittin exerts multiple effects on the release of free fatty acids from L1210 cells: lack of selective activation of phospholipase A2 by melittin. Archives of Biochemistry and Biophysics, 389(1), 57–67.PubMedCrossRef

95.

Mihajlovic, M., & Lazaridis, T. (2010). Antimicrobial peptides in toroidal and cylindrical pores. Biochimica et Biophysica Acta, 1798(8), 1485–1493.PubMedCrossRef

96.

Putz, T., Ramoner, R., Gander, H., Rahm, A., Bartsch, G., & Thurnher, M. (2006). Antitumor action and immune activation through cooperation of bee venom secretory phospholipase A2 and phosphatidylinositol-(3,4)-bisphosphate. Cancer Immunology, Immunotherapy, 55(11), 1374–1383.PubMedCrossRef

97.

Engers, R., & Gabbert, H. E. (2000). Mechanisms of tumor metastasis: cell biological aspects and clinical implications. Journal of Cancer Reserch and Clinical Oncology, 126, 682–692.CrossRef

98.

Lester, B. R., & McCarthy, J. B. (1992). Tumor cell adhesion to the extracellular matrix and signal transduction mechanisms implicated in tumor cell motility, invasion and metastasis. Cancer Metastasis Review, 11, 31–44.CrossRef

99.

Cho, H. J., Jeong, Y. J., Park, K. K., Park, Y. Y., Chung, I. K., Lee, K. G., Yeo, J. H., Han, S. M., Bae, Y. S., & Chang, Y. C. (2010). Bee venom suppresses PMA-mediated MMP-9 gene activation via JNK/p38 and NF-kappaB-dependent mechanisms. Journal of Ethnopharmacology, 127(3), 662–668.PubMedCrossRef

100.

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. (2010). Melittin suppresses PMA-induced tumor cell invasion by inhibiting NF-kappaB and AP-1-dependent MMP-9 expression. Molecular Cells, 29(2), 209–215.CrossRef

101.

Zetter, B. R. (1990). The cellular basis of site-specific tumor metastasis. The New England Journal of Medicine, 322, 605–612.PubMedCrossRef

102.

Tang, D. G., & Honn, K. V. (1994). Adhesion molecules and tumor metastasis: an update. Invasion & Metastasis, 14, 109–122.

103.

Kannagi, R. (1997). Carbohydrate-mediated cell adhesion involved in hematogenous metastasis of cancer. Glycoconjugate Journal, 14, 577–584.PubMedCrossRef

104.

Oršolić, N., & Bašić, I. (2003). Apoptosis and necrosis as possible mechanisms for antitumor activity of bee venom. Mellifera, 3, 34–42.

105.

Ćurić, S., Oršolić, N., Krsnik, B., Balenović, T., Valpotić, I., Sulimanović, Đ., & Bašić, I. (1993). Immune responses of a mouse to bee venom. Stočarstvo, 47, 131–136.

106.

Huh, J. E., Baek, Y. H., Lee, M. H., Choi, D. Y., Park, D. S., & Lee, J. D. (2010). Bee venom inhibits tumor angiogenesis and metastasis by inhibiting tyrosine phosphorylation of VEGFR-2 in LLC-tumor-bearing mice. Cancer Letters, 292(1), 98–110.PubMedCrossRef

107.

Ling, C. Q., Li, B., Zhang, C., Zhu, D. Z., Huang, X. Q., Gu, W., & Li, S. X. (2005). Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma. Annals of Oncology, 16(1), 109–115.PubMedCrossRef

108.

Hansel, W., Enright, F., & Leuschner, C. (2007). Destruction of breast cancers and their metastases by lytic peptide conjugates in vitro and in vivo. Molecular and Cellular Endocrinology, 260–262, 183–189.PubMedCrossRef

109.

Hansel, W., Leuschner, C., & Enright, F. (2007). Conjugates of lytic peptides and LHRH or betaCG target and cause necrosis of prostate cancers and metastases. Molecular and Cellular Endocrinology, 269, 26–33.PubMedCrossRef

110.

Kumar, C. S., Leuschner, C., Doomes, E. E., Henry, L., Juban, M., & Hormes, J. (2004). Efficacy of lytic peptide bound magnetite nanoparticles in destroying breast cancer cells. Journal of Nanoscience and Nanotechnology, 4, 245–249.PubMedCrossRef

111.

Jaynes, J. M., Julian, G. R., Jeffers, G. W., White, K. L., & Enright, F. M. (1989). Peptide Research, 2, 157–160.PubMed

112.

Moore, A. J., Devine, D. A., Bibby, M. C., Moore, A. J., Beazley, W. D., Bibby, M. C., & Devine, D. A. (1996). Antimicrobial activity of cecropins. Journal of Antimicrobial Chemotherapy, 37(6), 1077–1089.PubMedCrossRef

113.

Werkmeister, J. A., Kirkpatrick, A., McKenzie, J. A., & Rivett, D. E. (1993). The effect of sequence variations and structure on the cytolytic activity of melittin peptides. Biochimica et Biophysica Acta, 1157, 50–54.PubMedCrossRef

114.

Ferguson, E. L., & Duncan, R. (2009). Dextrin-phospholipase A2: synthesis and evaluation as a bioresponsive anticancer conjugate. Biomacromolecules, 10(6), 1358–1364.PubMedCrossRef

115.

Barrajón-Catalán, E., Menéndez-Gutiérrez, M. P., Falco, A., Carrato, A., Saceda, M., & Micol, V. (2010). Selective death of human breast cancer cells by lytic immunoliposomes: correlation with their HER2 expression level. Cancer Letters, 290(2), 192–203.PubMedCrossRef

116.

Baban, D. F., & Seymour, L. W. (1998). Control of tumor vascular permeability. Advanced Drug Delivery Reviews, 34, 109–119.PubMedCrossRef

117.

Shubik, P. (1982). Vascularization of tumors: a review. Journal of Cancer Reserch and Clinical Oncology, 103, 211–226.CrossRef

118.

Rubin, P., & Casarett, G. (1966). Microcirculation of tumors. I. Anatomy, function, and necrosis. Clinical Radiology, 17, 220–229.PubMedCrossRef

119.

Hobbs, S. K., Monsky, W. L., Yuan, F., Roberts, W. G., Griffith, L., Torchilin, V. P., & Jain, R. K. (1998). Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. The Proceedings of the National Academy of Sciences USA, 95, 4607–4612.CrossRef

120.

Soman, N. R., Baldwin, S. L., Hu, G., Marsh, J. N., Lanza, G. M., Heuser, J. E., Arbeit, J. M., & Wickline, S. A. (2009). Schlesinger PH. Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth. Journal of Clincal Investigation, 119(9), 2830–2842.CrossRef

121.

Holle, L., Song, W., Holle, E., Wei, Y., Li, J., Wagner, T. E., & Yu, X. (2009). In vitro- and in vivo-targeted tumor lysis by an MMP2 cleavable melittin-LAP fusion protein. International Journal of Oncology, 35(4), 829–835.PubMed

122.

Gawronska, B., Leuschner, C., Enright, F. M., & Hansel, W. (2002). Effects of a lytic peptide conjugated to beta HCG on ovarian cancer: studies in vitro and in vivo. Gynecologic Oncology, 85(1), 45–52.PubMedCrossRef

123.

Leuschner, C., Enright, F. M., Melrose, P. A., & Hansel, W. (2001). Targeted destruction of androgen-sensitive and -insensitive prostate cancer cells and xenografts through luteinizing hormone receptors. Prostate, 46, 116–126.PubMedCrossRef

124.

Hansel, W., Leuschner, C., Gawronska, B., & Enright, F. M. (2001). Targeted destruction of prostate cancer cells and xenografts by lytic peptide-LH. Reproductive Biology, 1, 20–32.PubMed

125.

Sancar, A., Lindsey-Boltz, L. A., Unsal-Kacmaz, K., & Linn, S. (2004). Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annual Review of Biochemistry, 73, 39–85.PubMedCrossRef

126.

Hait, W. N., Cadman, E., Benz, C., Cole, J., & Weiss, B. (1983). Inhibition of cyclic nucleotide phosphodiesterase and calmodulin. Proceedings of the American Association for Cancer Research, 2, 5–9.

127.

Hait, W. N., Grais, L., Benz, C., & Cadman, E. C. (1985). Inhibition of growth of leukemic cells by inhibitors of calmodulin: phenothiazines and melittin. Cancer Chemotherapy and Pharmacology, 14, 202–205.PubMedCrossRef

128.

Hait, W. N., & Lee, G. L. (1985). Characteristics of the cytotoxic effects of the phenothiazine class of calmodulin antagonists. Biochemical Pharmacology, 34(22), 3973–3978.PubMedCrossRef

129.

Okumara, K., Kato, T., Ito, J., & Tanaka, R. (1982). Inhibition by calmodulin antagonists of glioblast DNA synthesis and morphological changes induced by glial maturation factor. Developmental Brain Reserch, 255, 661–665.

130.

Means, A. R., Chafouleas, J. A., Lagace, L., Lai, E., & Stein, J. P. (1982). Multiple roles for calmodulin in the regulation of eukarryotic cell metabolism. In Gene regulation (pp. 307–326). New York: Academic.

131.

Chafouleas, J. G., Bolton, W. E., Hidaka, H., Boyd, A. E., & Means, A. R. (1982). Calmodulin and the cell cycle: involvement in regulation of cell cycle progression. Cell, 28, 41–50.PubMedCrossRef

132.

Gamapathi, R., & Grabowski, D. (1983). Enhancement of sensitivity to adriamyc in resistant P388 leukemia by the calmodulin inhibitor, trifluoperazine. Cancer Reserch, 43, 3696–3699.

133.

Rahmanzadeh, R., Rai, P., Celli, J. P., Rizvi, I., Baron-Lühr, B., Gerdes, J., & Hasan, T. (2010). Ki-67 as a molecular target for therapy in an in vitro three-dimensional model for ovarian cancer. Cancer Reserch, 70(22), 9234–9242.CrossRef

134.

Bullwinkel, J., Baron-Lühr, B., Lüdemann, A., Wohlenberg, C., Gerdes, J., & Scholzen, T. (2006). Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells. Journal of Cell Physiology, 206(3), 624–635.CrossRef

135.

Yang, Z. L., Ke, Y. Q., Xu, R. X., & Peng, P. (2007). Melittin inhibits proliferation and induces apoptosis of malignant human glioma cells. Nan Fang Yi Ke Da Xue Xue Bao, 27(11), 1775–1777.PubMed

136.

Balk, S. D., Polimeni, P. I., Hoon, B. S., Lestourgeon, D. N., & Mitchell, R. S. (1979). Proliferation of Rous sarcoma virus-infected, but not of normal chicken fibroblasts in a medium of reduced calcium and magnesium concentration. The Proceedings of the National Academy of Sciences USA, 76, 3913–3916.CrossRef

137.

Whitfield, J. F., Boynton, A. L., Macmanus, J. P., Sicorska, M., & Tsang, B. K. (1979). The regulation of cell proliferation by calcium and cyclic AMP. Molecular and Cellular Biochemistry, 27, 155–179.PubMedCrossRef

138.

Zhao, M., Brunk, U. T., & Eaton, J. W. (2001). Delayed oxidant-induced cell death involves activation of phospholipase A2. FEBS Letters, 509(3), 399–404.PubMedCrossRef

139.

Li, B., Li, L. Y., Luo, X., & Wang, X. (2001). Endonuclease G is an apoptotic DNase when released from mitochondria. Nature, 412, 95–99.PubMedCrossRef

140.

Miramar, M. D., Costantini, P., Ravagnan, L., Saraiva, L. M., Haouzi, D., Brothers, G., Penninger, J. M., Peleato, M. L., Kroemer, G., & Susin, S. A. (2001). NADH oxidase activity of mitochondrial apoptosis-inducing factor. Journal of Biological Chemistry, 276(19), 16391–16398.PubMedCrossRef

141.

Kroemer, G., & Martin, S. J. (2005). Caspase-independent cell death. Nature Medicine, 11(7), 725–730.PubMedCrossRef

142.

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. (2008). The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells. Vivo, 22(2), 237–245.

143.

Ip, SW., Wei, HC., Lin, JP., Kuo, HM., Liu, KC., Hsu, SC., Yang, JS., Mei-Dueyang, Chiu, TH., Han, SM., Chung, JG (2008a) Bee venom induced cell cycle arrest and apoptosis in human cervical epidermoid carcinoma Ca Ski cells. Anticancer Research, 28(2A), 833–842.

144.

Moon, D. O., Park, S. Y., Choi, Y. H., Kim, N. D., Lee, C., & Kim, G. Y. (2008). Melittin induces Bcl-2 and caspase-3-dependent apoptosis through downregulation of Akt phosphorylation in human leukemic U937 cells. Toxicon, 51(1), 112–120.PubMedCrossRef

145.

Wang, C., Chen, T., Zhang, N., Yang, M., Li, B., Lu, X., Cao, X., & Ling, C. (2009). Melittin, a major component of Bee Venom, sensitizes human hepatocellular carcinoma cells to TRAIL-induced apoptosis by activating CaMKII-TAK1-JNK/p38 and inhibiting IKK-NFkappa B. Journal of Biological Chemistry, 284(6), 3804–3813.PubMedCrossRef

146.

Grisotto, L. S., Mendes, G. E., Castro, I., Baptista, M. A., Alves, V. A., Yu, L., & Burdmann, E. A. (2006). Mechanisms of bee venom-induced acute renal failure. Toxicon, 48(1), 44–54.PubMedCrossRef

147.

Putz, T., Ramoner, R., Gander, H., Rahm, A., Bartsch, G., Bernardo, K., Ramsay, S., & Thurnher, M. (2007). Bee venom secretory phospholipase A2 and phosphatidylinositol-homologues cooperatively disrupt membrane integrity, abrogate signal transduction and inhibit proliferation of renal cancer cells. Cancer Immunology, Immunotherapy, 56(5), 627–640.PubMedCrossRef

148.

Andreae, S., Buisson, S., & Triebel, F. (2003). MHC class II signal transduction in human dendritic cells induced by a natural ligand, the LAG-3 protein (CD223). Blood, 102, 2130–2137.PubMedCrossRef

149.

Appel, S., Rupf, A., Weck, M. M., Schoor, O., Brummendorf, T. H., Weinschenk, T., Grunebach, F., & Brossart, P. (2005). Effects of imatinib on monocyte-derived dendritic cells are mediated by inhibition of nuclear factor-kappaB and Akt signaling pathways. Clinical Cancer Reserch, 11, 1928–1940.CrossRef

150.

Del Prete, A., Vermi, W., Dander, E., Otero, K., Barberis, L., Luini, W., Bernasconi, S., Sironi, M., Santoro, A., Garlanda, C., Facchetti, F., Wymann, M. P., Vecchi, A., Hirsch, E., Mantovani, A., & Sozzani, S. (2004). Defective dendritic cell migration and activation of adaptive immunity in I3Kgamma-deficient mice. EMBO Journal, 23, 3505–3515.PubMedCrossRef

151.

Payrastre, B., Missy, K., Giuriato, S., Bodin, S., Plantavid, M., & Gratacap, M. (2001). Phosphoinositides: key players in cell signalling, in time and space. Cellular Signalling, 13, 377–387.PubMedCrossRef

152.

Toker, A. (2002). Phosphoinositides and signal transduction. Cellular and Molecular Life Science, 59, 761–779.CrossRef

153.

Gille, H., & Downward, J. (1999). Multiple ras effector pathways contribute to G(1) cell cycle progression. Journal of Biological Chemistry, 274, 22033–22040.PubMedCrossRef

154.

Kennedy, S. G., Wagner, A. J., Conzen, S. D., Jordan, J., Bellacosa, A., Tsichlis, P. N., & Hay, N. (1997). The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes & Development, 11, 701–713.CrossRef

155.

Park, J. H., Kim, K. H., Kim, S. J., Lee, W. R., Lee, K. G., & Park, K. K. (2010). Bee venom protects hepatocytes from tumor necrosis factor-alpha and actinomycin D.Archives. Pharmacological Reserch, 33(2), 215–223.

156.

Wang, W., & El-Deiry, W. S. (2008). Restoration of p53 to limit tumor growth. Current Opinion in Oncology, 20(1), 90–96.PubMedCrossRef

157.

Wiman, K. G. (2010). Pharmacological reactivation of mutant p53: from protein structure to the cancer patient. Oncogene, 29(30), 4245–4252.PubMedCrossRef

158.

Vousden, K. H., & Lane, D. P. (2007). p53 in health and disease. Nature Reviews Molecular Cell Biology, 8, 275–283.PubMedCrossRef

159.

Shangary, S., Qin, D., McEachern, D., Liu, M., Miller, R. S., Qiu, S., Nikolovska-Coleska, Z., Ding, K., Wang, G., Chen, J., Bernard, D., Zhang, J., Lu, Y., Gu, Q., Shah, R. B., Pienta, K. J., Ling, X., Kang, S., Guo, M., Sun, Y., Yang, D., & Wang, S. (2008). Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. The Proceedings of the National Academy of Sciences USA, 105, 3933–3938.CrossRef

160.

Li, C., Pazgier, M., Liu, M., Lu, W. Y., & Lu, W. (2009). Apamin as a template for structure-based rational design of potent peptide activators of p53. Angewandte Chemie International Edition in English, 48(46), 8712–8715.CrossRef

161.

Stocker, M. (2004). Ca(2+)-activated K+ channels: molecular determinants and function of the SK family. Nature Reviews Neuroscience, 5, 758–770.PubMedCrossRef

162.

Bykov, V. J., Issaeva, N., Shilov, A., Hultcrantz, M., Pugacheva, E., Chumakov, P., Bergman, J., Wiman, K. G., & Selivanova, G. (2002). Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nature Medicine, 8(3), 282–288.PubMedCrossRef

163.

Tongyoo, A. (2010). Targeted therapy: novel agents against cancer. Journal of the Medical Association of Thailand, 93(Suppl 7), S311–S323. Review.PubMed

164.

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–674. Review.PubMedCrossRef

165.

Song CC, Lu X, Cheng BB, DU J, Li B, Ling CQ. (2007) Effects of melittin on growth and angiogenesis of human hepatocellular carcinoma BEL-7402 cell xenografts in nude mice. Ai Zheng, 26(12), 1315–1322.

166.

Weng, C. J., Chau, C. F., Yen, G. C., Liao, J. W., Chen, D. H., & Chen, K. D. (2009). Inhibitory effects of ganoderma lucidum on tumorigenesis and metastasis of human hepatoma cells in cells and animal models. Journal of Agricultural and Food Chemistry, 57(11), 5049–5057.PubMedCrossRef

167.

Kato, Y., Yamashita, T., & Ishikawa, M. (2002). Relationship between expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and invasion ability of cervical cancer cells. Oncology Reports, 9(3), 565–569.PubMed

168.

Liotta, L. A., & Stetler-Stevenson, W. G. (1991). Tumor invasion and metastasis: an imbalance of positive and negative regulation. Cancer Research, 51(18 Suppl)), 5054s–5059s. Review.PubMed

169.

Rahman, K. M., Sarkar, F. H., Banerjee, S., Wang, Z., Liao, D. J., Hong, X., & Sarkar, N. H. (2006). Therapeutic intervention of experimental breast cancer bone metastasis by indole-3-carbinol in SCID-human mouse model. Molecular Cancer Therapeutics, 5(11), 2747–2756.PubMedCrossRef

170.

Nabeshima, K., Inoue, T., Shimao, Y., & Sameshima, T. (2002). Matrix metalloproteinases in tumor invasion: role for cell migration. Pathology International, 52(4), 255–264. Review.PubMedCrossRef

171.

Bhoopathi, P., Chetty, C., Kunigal, S., Vanamala, S. K., Rao, J. S., & Lakka, S. S. (2008). Blockade of tumor growth due to matrix metalloproteinase-9 inhibition is mediated by sequential activation of beta1-integrin, ERK, and NF-kappaB. Journal of Biological Chemistry, 283(3), 1545–1552.PubMedCrossRef

172.

Hamedani, M., Mirshafiey, A., Vatanpour, H., Khorramizadeh, M., Saadat, F., Berahmeh, A., & Hadji-Ghasemi, F. (2005). In vitro assessment of bee venom effects on matrix metalloproteinase activity and interferon production. Iranian Journal of Allergy, Asthma, and Immunology, 4(1), 9–14.PubMed

173.

Hamedani, M., Vatanpour, H., Saadat, F., Reza Khorramizaheh, M., & Mirshafiey, A. (2005). Bee venom, immunostimulant or immunosuppressor? Insight into the effect on matrix metalloproteinases and interferons. Immunopharmacology and Immunotoxicology, 27(4), 671–681.PubMedCrossRef

174.

Nam, S., Ko, E., Park, S. K., Ko, S., Jun, C. Y., Shin, M. K., Hong, M. C., & Bae, H. (2005). Bee venom modulates murine Th1/Th2 lineage development. International Immunopharmacology, 5(9), 1406–1414.PubMedCrossRef

175.

Leitinger, N. (2003). Oxidized phospholipids as modulators of inflammation in atherosclerosis. Current Opinion in Lipidology, 14, 421–430.PubMedCrossRef

176.

Banchereau, J., & Steinman, R. M. (1998). Dendritic cells and the control of immunity. Nature, 392, 245–252.PubMedCrossRef

177.

Matzinger, P. (2002). The danger model: a renewed sense of self. Science, 296, 301–305.PubMedCrossRef

178.

Hartman Hartman, D. A., Tomchek, L. A., Lugay, J. R., Lewin, A. C., Chau, T. T., & Carlson, R. P. (1991). Comparison of antiinflammatory and antiallergic drugs in the melittin- and D49 PLA2-induced mouse paw edema models. Agents and Actions, 34(1–2), 84–88.CrossRef

179.

Lariviere, W. R., & Melzack, R. (1996). The bee venom test: a new tonic-pain test. Pain, 66(2–3), 271–277.PubMedCrossRef

180.

Schneider, H., & Urbanek, R. (1984). Humoral and cellular immune response of the rat to immunization with bee venom. Clinical and Experimental Immunology, 57, 449–453.PubMed

181.

Magnan, A., Marin, V., Mely, L., Birnbaum, J., Romanet, S., Bongrand, P., & Vervloet, D. (2001). Venom immunotherapy induces monocyte activation. Clinical and Experimental Allergy, 31(8), 1303–1309.PubMedCrossRef

182.

Ribardo, D. A., Kuhl, K. R., Peterson, J. W., & Chopra, A. K. (2002). Role of melitin- like region within phospholipase A2-activating protein in biological function. Toxicon, 40, 519–526.PubMedCrossRef

183.

Rekka, E., Kourounakis, L., & Kourounakis, P. (1990). Antioxidant activity of interleukin production affected by honeybee venom. Arzneimittel-Forschung, 40, 912–913.PubMed

Title: Bee venom in cancer therapy
Author: Nada Oršolić
Publication date: 01-06-2012
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 1-2/2012
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-011-9339-3

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Image Credits

ASCO 2024 | Highlights of the Day: Breast cancer – metastatic/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Gynecologic Cancer/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Breast Cancer – local/regional/adjuvant/© 2024 American Society of Clinical Oncology, all rights reserved., Melanoma/© selvanegra / Getty Images / iStock, Antibody drug conjugated with cytotoxic payload/© Love Employee / Getty images / iStock

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1-2/2012

Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression

The present and future of gene profiling in breast cancer

The Eph/Ephrin family in cancer metastasis: communication at the service of invasion

Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: a review of mechanisms

Gastroenteropancreatic neuroendocrine tumor cancer stem cells: do they exist?