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Co-culture with NK-92MI cells enhanced the anti-cancer effect of bee venom on NSCLC cells by inactivation of NF-κB

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Abstract

In the present study we experimented on a multimodal therapeutic approach, such as combining chemotherapy agent (Bee venom) with cellular (NK-92MI) immunotherapy. Previously bee venom has been found to show anti-cancer effect in various cancer cell lines. In lung cancer cells bee venom showed an IC50 value of 3 μg/ml in both cell lines. The co-culture of NK-92MI cell lines with lung cancer cells also show a decrease in viability upto 50 % at 48 h time point. Hence we used bee venom treated NK-92MI cells to co-culture with NSCLC cells and found that there is a further decrease in cell viability upto 70 and 75 % in A549 and NCI-H460 cell lines respectively. We further investigated the expression of various apoptotic and anti-apoptotic proteins and found that Bax, cleaved caspase-3 and -8 were increasing where as Bcl-2 and cIAP-2 was decreasing. The expression of various death receptor proteins like DR3, DR6 and Fas was also increasing. Concomitantly the expression of various death receptor ligands (TNFalpha, Apo3L and FasL) was also increasing of NK-92MI cells after co-culture. Further the DNA binding activity and luciferase activity of NF-κB was also inhibited after co-culture with bee venom treated NK-92MI cell lines. The knock down of death receptors with si-RNA has reversed the decrease in cell viability and NF-κB activity after co-culture with bee venom treated NK-92MI cells. Thus this new approach can enhance the anti-cancer effect of bee venom at a much lower concentration.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. MRC, 2008-0062275), and by the Ministry of Trade, Industry, & Energy (MOTIE, 141526993) through fostering project of Osong Academy-Industry Convergence (BAIO).

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The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Ch’ongju, Chungbuk, 361-763, Korea

    Pushpa Saranya Kollipara, Dohee Won, Sang Min Lee, Ha Chang Sung, Hyun Sok Chang, Kang Tae Lee, Kang Sik Lee, Mi Hee Park & Jin Tae Hong

  2. Department of Obstetrics and Gynecology, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Min Jong Song

  3. College of Korean Medicine, Gachon University, 65 Bukjeong-Dong, Sujeong-gu, Songnam, Gyeonggi, 461-701, Korea

    Jung Hyun Kim & Ho Sueb Song

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  1. Pushpa Saranya Kollipara
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  2. Jung Hyun Kim
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  3. Dohee Won
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  4. Sang Min Lee
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  12. Jin Tae Hong
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Correspondence to Ho Sueb Song or Jin Tae Hong.

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Kollipara, P.S., Kim, J.H., Won, D. et al. Co-culture with NK-92MI cells enhanced the anti-cancer effect of bee venom on NSCLC cells by inactivation of NF-κB. Arch. Pharm. Res. 37, 379–389 (2014). https://doi.org/10.1007/s12272-013-0319-8

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  • DOI: https://doi.org/10.1007/s12272-013-0319-8

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