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Anti‐cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF‐κB
Author(s) -
Park Mi Hee,
Choi Myoung Suk,
Kwak Dong Hoon,
Oh KiWan,
Yoon Do Young,
Han Sang Bae,
Song Ho Sueb,
Song Min Jong,
Hong Jin Tae
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21296
Subject(s) - melittin , du145 , lncap , apoptosis , prostate cancer , medicine , cancer cell , programmed cell death , bee venom , cancer research , cancer , pharmacology , biology , immunology , biochemistry , peptide , zoology
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 T o 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. RESULTS AND 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. Prostate 71:801–812, 2011. © 2010 Wiley‐Liss, Inc.