title: Anti-cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF-κB.
abstract: BACKGROUND
  Bee venom has been used as a traditional medicine to treat arthritis, rheumatism, back pain, cancerous tumors, and skin diseases. However, the effects of bee venom on the prostate cancer and their action mechanisms have not been reported yet.
  
  
  METHODS
  To determine the effect of bee venom and its major component, melittin on the prostate cancer cells, apoptosis is analyzed by tunnel assay and apoptotic gene expression. For xenograft studies, bee venom was administrated intraperitoneally twice per week for 4 weeks, and the tumor growth was measured and the tumor were analyzed by immunohistochemistry. To investigate whether bee venom and melittin can inactivate nuclear factor kappa B (NF-κB), we assessed NF-κB activity in vitro and in vivo.
  
  
  CONCLUSIONS
  Bee venom (1-10 µg/ml) and melittin (0.5-2.5 µg/ml) inhibited cancer cell growth through induction of apoptotic cell death in LNCaP, DU145, and PC-3 human prostate cancer cells. These effects were mediated by the suppression of constitutively activated NF-κB. Bee venom and melittin decreased anti-apoptotic proteins but induced pro-apoptotic proteins. However, pan caspase inhibitor abolished bee venom and melittin-induced apoptotic cell death and NF-κB inactivation. Bee venom (3-6 mg/kg) administration to nude mice implanted with PC-3 cells resulted in inhibition of tumor growth and activity of NF-κB accompanied with apoptotic cell death. Therefore, these results indicated that bee venom and melittin could inhibit prostate cancer in in vitro and in vivo, and these effects may be related to NF-κB/caspase signal mediated induction of apoptotic cell death.
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, Korea.
authors: Mi Hee
authors: MH
authors: Park
authors: Myoung Suk
authors: MS
authors: Choi
authors: Dong Hoon
authors: DH
authors: Kwak
authors: Ki-Wan
authors: KW
authors: Oh
authors: Do Young
authors: DY
authors: Yoon
authors: Sang Bae
authors: SB
authors: Han
authors: Ho Sueb
authors: HS
authors: Song
authors: Min Jong
authors: MJ
authors: Song
authors: Jin Tae
authors: JT
authors: Hong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors; D001514:Bee Venoms / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D008555:Melitten / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001514:Bee Venoms; D016328:NF-kappa B; D008555:Melitten; D020169:Caspases