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1391 - -

11. Park. M. H. Park. S.Y, Kwak. D. H, Oh. L. Y, Yoon. D. Y, Han. S. B, Song. H. S, Hong. J. T. (2010). Anti-cancer
effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NNF-Kb.
Prostate.
12. Park. H. L,Lee.S. H, Son. D. J, Oh. K. W, Kim. K. H, Song. H. S. (2004). Anti-arthritic effect of bee
venom:inhibition of inflammation mediator generation by suppression of NF-KappaB through interaction
with p50 subunit, Arthritis Rheum,3515-3504:)11(50 Nada Or Oli .(2003)

1391 - -

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in in vivo 2010 Park
NF-kB/caspase . vitro
.)2010,.park et al(

. ) Natural Products (

13. Son. D. J, Lee. Y. H, Songb. H. S, Leea. C. K, Hong. J. T. (2007). Therapeutic application of Anti-arthritis,Painreleasing and anti-cancer Effect of bee venom And its Constituent Compounds. Pharmacology and
Therapeutics,270-246:)2( 115
14. Son. D. J,Ha. H. J, Songb. 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. (2006) Mellitin inhibits Vascular Smooth Muscle cell Proliferation Through Induction of Apoptosis
via Suppression of Nuclear Factor-kB and Akt Activation and Enhancement of Apoptotic Protein Expression.
PharmacologyandExperimental Therapeutics,634-627:)2(317
15. Sub. S. J, Kim. K. S, Kim. M. J, Chang. Y .C, Lee.S. D, Kim. M. S, Kwon. D. Y, Kim. C.H.(2006). Effect of
bee venom on protease activities and free radical damages in synovial fluid from type II collagen-induced
rheumatoid arthritis rats. Toxicology in vitro, 1471-20:1465
16. Terra.R. M,Guimaraes J.A, Verli H. (2007). Structural and Functional behavior of biologically active
monomeric mellitin. Molecular graphics and modeling,772-767:)6(25
17. Tu W.C, Wu. C. C, Hsieh L. H, Chen. Y. C. (2008) Honeybee venom induces calcium- dependent but
caspase-independent apoptotic cell death in human melanoma A2058 cells.Toxcicon329-52:318
- - .)1373( -18
11597 4

:
1.Chu.T, chang H.H, Huang C.J, chang H.c, chi C.C, H.H.(2007). Phospholipase A2 independent Ca2+ entry
and subsequent apoptosis indused by melitin in human MG63 osteosarcoma cells,life science,369-364 :)40( 80.
2.HongS.J. Rim G.S, Tang H.I, Yin C.S,. Koh H.G, Jang M.H.(2005). Bee venom induces apoptosis through
caspase3- activation in synovial fibroblasts of patient with rheumatoid arthritis, Toxicon, 45-39 :)1( 46.
3.IP S.W,Wei H.C, Lin J.P, Kuo H.M,Liu K.C, Hsu S.C, Yang J.S, Mei-Dueyang, Chi T.H, Chang J.G. (2008).
Bee venom induced cell cycle arrest and apoptosis in human cervical epidernoid carcinoma Ca Ski cells.
Anticancer Research, 842-833: 28.
4.JangM.H, Shin M.C, Sabina L.S, Han S. N, Park. H. J, Insop. S.I, Lee. J.S, Kim. K. A, Kim. E.H, kim. C. J. (2003)
Bee venom induces Apoptosis and InhibitsExpression of Cyclooxygenase2- mRNA in Human Lung Cancer
Cell line NCI-HI299. Pharmacology science ,104-95 :91.
5. Kwon.Y.B, Lee. J. D, 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 response. Pain,280-90:271
6. Lee. Y. J, Kang. S.J, Kim. B. M, Kim.Y. J, Woo. H. D, Chung. H. w. (2007). Cytotoxicity of honeybee
(Apismellifera) venom in normal human lymphocytes and HL60- cells. Chemico-Biological Interaction,
171-10:157
7. Mirshafiey Abbas. (2007). Venom Therapy in multiple sclerosis. Neuropharmacology, XX:9-1.
8. Moon. D. O, Park. S. Y, Heo M.S, Kim. K.C, Park C, Ko. W. S.(2006)Key reguators in bee venom induced
apoptosis areBcl2- and caspase3-in human leukemic U937 cells through down regulation of ERK and Akt. Int
Immonopharmaco1807-1796: 1,6
9. Moon. D. O, Park. S. Y, Choi. Y. H, Kim. N.D.(2008) Mellitin induces Bcl2- and caspase-3 dependent apoptosis
through down regulation of Akt phosphorylation in human leukemic U937 cells. Toxcicion,120-51:112
10. Nada Or Oli. (2003). Inhibition of mammary carcinoma cell proliferation in vitro and tumor growth in
vivo by bee venom. Toxcicion,870-861:)7(41.

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