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Cancer Cell Growth Inhibitory Effect of Bee Venom via Increase of Death Receptor 3 Expression and Inactivation of NF-kappa B in NSCLC Cells

1
College of Pharmacy and Medical Research Center, Chungbuk National University, 52 Naesudong-ro, Heungdeok-gu, Cheongju, Chungbuk 361-763, Korea
2
Department of Obstetrics and Gynecology, Daejeon St. Mary's Hospital, College of Medicine, the Catholic University of Korea, 64 Daeheung-ro, Jung-gu, Daejeon 301-723, Korea
3
College of Oriental Medicine, Gachon University, San 65, Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggii 461-701, Korea
*
Author to whom correspondence should be addressed.
Toxins 2014, 6(8), 2210-2228; https://doi.org/10.3390/toxins6082210
Received: 8 April 2014 / Revised: 16 June 2014 / Accepted: 18 July 2014 / Published: 25 July 2014
(This article belongs to the Section Animal Venoms)
Our previous findings have demonstrated that bee venom (BV) has anti-cancer activity in several cancer cells. However, the effects of BV on lung cancer cell growth have not been reported. Cell viability was determined with trypan blue uptake, soft agar formation as well as DAPI and TUNEL assay. Cell death related protein expression was determined with Western blotting. An EMSA was used for nuclear factor kappaB (NF-κB) activity assay. BV (1–5 μg/mL) inhibited growth of lung cancer cells by induction of apoptosis in a dose dependent manner in lung cancer cell lines A549 and NCI-H460. Consistent with apoptotic cell death, expression of DR3 and DR6 was significantly increased. However, deletion of DRs by small interfering RNA significantly reversed BV induced cell growth inhibitory effects. Expression of pro-apoptotic proteins (caspase-3 and Bax) was concomitantly increased, but the NF-κB activity and expression of Bcl-2 were inhibited. A combination treatment of tumor necrosis factor (TNF)-like weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, docetaxel and cisplatin, with BV synergistically inhibited both A549 and NCI-H460 lung cancer cell growth with further down regulation of NF-κB activity. These results show that BV induces apoptotic cell death in lung cancer cells through the enhancement of DR3 expression and inhibition of NF-κB pathway. View Full-Text
Keywords: bee venom; apoptosis; death receptors; NF-κB bee venom; apoptosis; death receptors; NF-κB
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Choi, K.E.; Hwang, C.J.; Gu, S.M.; Park, M.H.; Kim, J.H.; Park, J.H.; Ahn, Y.J.; Kim, J.Y.; Song, M.J.; Song, H.S.; Han, S.-B.; Hong, J.T. Cancer Cell Growth Inhibitory Effect of Bee Venom via Increase of Death Receptor 3 Expression and Inactivation of NF-kappa B in NSCLC Cells. Toxins 2014, 6, 2210-2228.

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