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

Article information

Acupunct. 2016;33(2):1-9
Department of Acupuncture & Moxibustion Medicine, College of Oriental Medicine, Gachon University
*Corresponding author: Department of Acupuncture & Moxibustion Medicine, Gil Oriental Medical Hospital 21, Keunumul-ro, Jung-gu, Incheon, Republic of Korea, Tel: +82-32-770-1300, E-mail: hssong70@gachon.ac.kr
Received 2016 March 25; Revised 2016 May 22; Accepted 2016 May 23.

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

Fig. 2

Snake Venom Toxin enhances the expression of death receptor and its related apoptotic proteins by NK-92 cells in NCI H358 Cells

Fig. 3

Snake Venom Toxin decreased the expression of anti-apoptotic NF-κB and its signal molecules in NCI-H358 Cells

Fig. 4

NK-92 cells exerted cytotoxic effect on NCI H358 Cells through increasing NO concentration

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Article information Continued

Fig. 1

Snake Venom Toxin enhances cytotoxic effect of NK-92 cells on NCI H358 Cells

Fig. 2

Snake Venom Toxin enhances the expression of death receptor and its related apoptotic proteins by NK-92 cells in NCI H358 Cells

Fig. 3

Snake Venom Toxin decreased the expression of anti-apoptotic NF-κB and its signal molecules in NCI-H358 Cells

Fig. 4

NK-92 cells exerted cytotoxic effect on NCI H358 Cells through increasing NO concentration