Snake Venom synergized Cytotoxic Effect of Natural Killer Cells on NCI H358 Human Lung Cancer Cell Growth through Induction of Apoptosis

Abstract

Objectives : I investigated whether snake venom can synergistically strengthen the cytotoxic effects of NK-92 cells, and enhance the inhibition of the growth of lung cancer cells including NCI-H358 through the induction of death receptor dependent extrinsic apoptosis. Methods : Snake venom toxin inhibited cell growth of NCI-H358 Cells and exerted non influence on NK-92 cell viability. Moreover, when they were co-cultured with NK cells and concomitantly treated with 4 ㎍/㎖ of snake venom toxin, more influence was exerted on the inhibition of growth of NCI-H358 cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2 and DR3 and in NCI-H358 lung cancer cells was significantly increased by co-culture of NK-92 cells and treatment of 4 ㎍/㎖ of snake venom toxin, compared to co-culture of NK-92 cells alone. Coincidentally, Bax, caspase-3 and caspase- 8 - expressions of pro-apoptotic proteins in the extrinsic apoptosis pathway, demonstrated significant increase. However, in anti-apoptotic NF-κB activities, activity of the signal molecule was significantly decreased by co-culture of NK-92 cells and treatment of 4 ㎍/㎖ of snake venom toxin, compared to co-culture of NK-92 cells or snake venom toxin treated by NCIH358 alone. Meanwhile, in terms of NO generation, there is a significant increase, in co-culture of NK-92 cells with NCI-H358 cells as well as the co-culture of NK-92 cells and concomitant treatment of 4 ㎍/㎖ of snake venom toxin. However, no synergistic increase of NO generation was shown in co-culture of NK-92 cells and treatment of 4 ㎍/㎖ of snake venom toxin, compared to co-culture of NK-92 cells with NCI-H358 cells. Conclusion : Consequently, this data provides that snake venom toxin could be useful candidate compounds to suppress lung cancer growth along with the cytotoxic effect of NK-92 cells through extrinsic apoptosis.