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J Acupunct Res > Volume 33(2); 2016 > Article
Oh and Song: 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 μg/mℓ 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 μg/mℓ 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-κ B activities, activity of the signal molecule was significantly decreased by co-culture of NK-92 cells and treatment of 4 μg/mℓ of snake venom toxin, compared to co-culture of NK-92 cells or snake venom toxin treated by NCI-H358 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 μg/mℓ of snake venom toxin. However, no synergistic increase of NO generation was shown in co-culture of NK-92 cells and treatment of 4 μg/mℓ 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.

Fig. 1
Snake Venom Toxin enhances cytotoxic effect of NK-92 cells on NCI H358 Cells
acup-33-2-1f1.jpg
Fig. 2
Snake Venom Toxin enhances the expression of death receptor and its related apoptotic proteins by NK-92 cells in NCI H358 Cells
acup-33-2-1f2.gif
Fig. 3
Snake Venom Toxin decreased the expression of anti-apoptotic NF-κB and its signal molecules in NCI-H358 Cells
acup-33-2-1f3.gif
Fig. 4
NK-92 cells exerted cytotoxic effect on NCI H358 Cells through increasing NO concentration
acup-33-2-1f4.gif

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