Bee Venom Enhanced Cytotoxic Effect of Natural Killer Cells on Human Lung Cancer Through Inducing Extrinsic Apoptosis

Objectives : I investigated whether Bee Venom can synergistically strengthen the cytotoxic effects of NK-92 cells, enhancing the inhibition of the growth of Lung Cancer Cells including A549 and NCI-H460 through induction of death receptor dependent extrinsic apoptosis and NO generation in the Nitro-oxide pathway. Methods : Bee Venom inhibited cell proliferation of A549 or NCI-H460 Human Lung Cancer Cells as well as NK-92 Cells. Moreover, when they were co-punctured with NK cells and concomitantly treated by 3 ${\mu}g/ml$ of Bee Venom, more influence was exerted on inhibition of proliferation of A549 or NCI-H460 Human Lung Cancer Cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2, DR3, DR6 in A549 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells and treatment of 3 ${\mu}g/ml$ of Bee Venom, compared to co-culture of NK-92 cells alone, whereas the expression of Fas, TNFR2, DR6 in NCI-H460 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells, representing no synergistic effects in the co-culture of NK-92 cell and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom. Coincidently, caspase-8, a expression of pro-apoptotic proteins in the extrinsic apoptosis pathway demonstrated same results as the above. Meanwhile, In NO generation, there is little change of NO generation in co-culture of NK-92 cells with A549 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, whereas increase of NO generation was shown in co-culture of NK-92 cells with NCI-H460 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, although synergistic effects by Bee Venom was not found. Conclusions : These present data provide that Bee Venom could be useful candidate compounds to enhance lung cancer growth inhibiting ability of NK-92 cells through DR expression and the related apoptosis.