DOI QR코드

DOI QR Code

Enhanced Anti-Cancer Effect of Snake Venom Activated NK Cells on Lung Cancer Cells by Inactivation of NF-κB

  • Kollipara, Pushpa Saranya (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Won, Do Hee (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Hwang, Chul Ju (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Jung, Yu Yeon (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Yoon, Heui Seoung (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Park, Mi Hee (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Song, Min Jong (Department of Obstetrics and Gynecology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Song, Ho Sueb (College of Korean Medicine, Gachon University) ;
  • Hong, Jin Tae (College of Pharmacy and Medical Research Center, Chungbuk National University)
  • Received : 2013.11.27
  • Accepted : 2014.02.11
  • Published : 2014.03.31

Abstract

In the present study, we investigated anti-cancer effect of snake venom activated NK cells (NK-92MI) in lung cancer cell lines. We used snake venom ($4{\mu}g/ml$) treated NK-92MI cells to co-culture with lung cancer cells. There was a further decrease in cancer cell growth up to 65% and 70% in A549 and NCI-H460 cell lines respectively, whereas 30-40% was decreased in cancer cell growth by snake venom or NK-92MI alone treatment. We further found that the expression of various apoptotic proteins such as that Bax, and cleaved caspase-3 as well as the expression of various death receptor proteins like DR3, DR4 and Fas was also further increased. Moreover, consistent with cancer cell growth inhibition, the DNA binding activity of NF-${\kappa}B$ was also further inhibited after treatment of snake venom activated NK-92MI cells. Thus, the present data showed that activated NK cells could further inhibit lung cancer cell growth.

Keywords

References

  1. Al-Sadoon, M. K., Rabah, D. M. and Badr, G. (2013) Enhanced anticancer efficacy of snake venom combined with silica nanoparticles in a murine model of human multiple myeloma: molecular targets for cell cycle arrest and apoptosis induction. Cell. Immunol. 284, 129-138. https://doi.org/10.1016/j.cellimm.2013.07.016
  2. Ashkenazi, A. (2008) Targeting the extrinsic apoptosis pathway in cancer. Cytokine Growth Factor Rev. 19, 325-331. https://doi.org/10.1016/j.cytogfr.2008.04.001
  3. Badr, G., Al-Sadoon, M. K. and Rabah, D. M. (2013) Therapeutic efficacy and molecular mechanisms of snake (Walterinnesia aegyptia) venom-loaded silica nanoparticles in the treatment of breast cancer- and prostate cancer-bearing experimental mouse models. Free Radic. Biol. Med. 65, 175-189. https://doi.org/10.1016/j.freeradbiomed.2013.06.018
  4. Bae, J. H., Kim, J. Y., Kim, M. J., Chang, S. H., Park, Y. S., Son, C. H., Park, S. J., Chung, J. S., Lee, E. Y., Kim, S. H. and Kang, C. D. (2010) Quercetin enhances susceptibility to NK cell-mediated lysis of tumor cells through induction of NKG2D ligands and suppression of HSP70. J. Immunother. 33, 391-401. https://doi.org/10.1097/CJI.0b013e3181d32f22
  5. Bae, J. H., Kim, S. J., Kim, M. J., Oh, S. O., Chung, J. S., Kim, S. H. and Kang, C. D. (2012) Susceptibility to natural killer cell-mediated lysis of colon cancer cells is enhanced by treatment with epidermal growth factor receptor inhibitors through UL16-binding protein-1 induction. Cancer Sci. 103, 7-16. https://doi.org/10.1111/j.1349-7006.2011.02109.x
  6. Baud, V. and Karin, M. (2009) Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat. Rev. Drug Discov. 8, 33-40. https://doi.org/10.1038/nrd2781
  7. Brady, J., Carotta, S., Thong, R. P., Chan, C. J., Hayakawa, Y., Smyth, M. J. and Nutt, S. L. (2010) The interactions of multiple cytokines control NK cell maturation. J. Immunol. 185, 6679-6688. https://doi.org/10.4049/jimmunol.0903354
  8. Burke, S., Lakshmikanth, T., Colucci, F. and Carbone, E. (2010) New views on natural killer cell-based immunotherapy for melanoma treatment. Trends Immunol. 31, 339-345. https://doi.org/10.1016/j.it.2010.06.003
  9. Cerwenka, A. and Lanier, L. L. (2001) Natural killer cells, viruses and cancer. Nat. Rev. Immunol. 1, 41-49. https://doi.org/10.1038/35095564
  10. Cooper, M. A., Fehniger, T. A. and Caligiuri, M. A. (2001) The biology of human natural killer-cell subsets. Trends Immunol. 22, 633-640. https://doi.org/10.1016/S1471-4906(01)02060-9
  11. Du, G., Ye, L., Zhang, G., Dong, Q., Liu, K. and Tian, J. (2012) Human IL18-IL2 fusion protein as a potential antitumor reagent by enhancing NK cell cytotoxicity and IFN-gamma production. J. Cancer Res. Clin. Oncol. 138, 1727-1736. https://doi.org/10.1007/s00432-012-1248-5
  12. Elrod, H. A. and Sun, S. Y. (2008) Modulation of death receptors by cancer therapeutic agents. Cancer Biol. Ther. 7, 163-173. https://doi.org/10.4161/cbt.7.2.5335
  13. Glas, R., Franksson, L., Une, C., Eloranta, M. L., Ohlen, C., Orn, A. and Karre, K. (2000) Recruitment and activation of natural killer (NK) cells in vivo determined by the target cell phenotype. An adaptive component of NK cell-mediated responses. J. Exp. Med. 191, 129-138. https://doi.org/10.1084/jem.191.1.129
  14. Hercend, T., Farace, F., Baume, D., Charpentier, F., Droz, J. P., Triebel, F. and Escudier, B. (1990) Immunotherapy with lymphokine-activated natural killer cells and recombinant interleukin-2: a feasibility trial in metastatic renal cell carcinoma. J. Biol. Response Mod. 9, 546-555.
  15. Inoue, N., Matsuda, F., Goto, Y. and Manabe, N. (2011) Role of cell-death ligand-receptor system of granulosa cells in selective follicular atresia in porcine ovary. J. Reprod. Dev. 57, 169-175. https://doi.org/10.1262/jrd.10-198E
  16. Jahangeer, S., Forde, P., Soden, D. and Hinchion, J. (2013) Review of current thermal ablation treatment for lung cancer and the potential of electrochemotherapy as a means for treatment of lung tumours. Cancer Treat. Rev. 39, 862-871. https://doi.org/10.1016/j.ctrv.2013.03.007
  17. Jo, M., Park, M. H., Kollipara, P. S., An, B. J., Song, H. S., Han, S. B., Kim, J. H., Song, M. J. and Hong, J. T. (2012) Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicol. Appl. Pharmacol. 258, 72-81. https://doi.org/10.1016/j.taap.2011.10.009
  18. Kang, Y. J., Kim, I. Y., Kim, E. H., Yoon, M. J., Kim, S. U., Kwon, T. K. and Choi, K. S. (2011) Paxilline enhances TRAIL-mediated apoptosis of glioma cells via modulation of c-FLIP, survivin and DR5. Exp. Mol. Med. 43, 24-34. https://doi.org/10.3858/emm.2011.43.1.003
  19. Karin, M. and Greten, F. R. (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 5, 749-759. https://doi.org/10.1038/nri1703
  20. Karin, M. and Lin, A. (2002) NF-kappaB at the crossroads of life and death. Nat. Immunol. 3, 221-227.
  21. Latz, C., Huang, Q., Kapadia, M. K. and Freitag, S. K. (2009) Metastasis to eyelid as initial presentation of non-small cell carcinoma. Ophthal. Plast. Reconstr. Surg. 25, 406-408. https://doi.org/10.1097/IOP.0b013e3181b3b3df
  22. Magne, N., Bay, J. O., Blay, J. Y., Goncalves, A., Massard, C., Thariat, J., Wislez, M., Andre, T. and Vignot, S. (2012) [American Society of Clinical Oncology (ASCO) 2012 essential data: the editorial board of the Bulletin du Cancer point of view]. Bull. Cancer 99, 1209-1217.
  23. Markovic, S. N. and Murasko, D. M. (1991) Role of natural killer and T-cells in interferon induced inhibition of spontaneous metastases of the B16F10L murine melanoma. Cancer Res. 51, 1124-1128.
  24. Mohammed, N., Kestin, L. L., Grills, I. S., Battu, M., Fitch, D. L., Wong, C. Y., Margolis, J. H., Chmielewski, G. W. and Welsh, R. J. (2011) Rapid disease progression with delay in treatment of non-small-cell lung cancer. Int. J. Radiat. Oncol. Biol. Phys. 79, 466-472. https://doi.org/10.1016/j.ijrobp.2009.11.029
  25. Nakshatri, H., Bhat-Nakshatri, P., Martin, D. A., Goulet, R. J., Jr. and Sledge, G. W., Jr. (1997) Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol. Cell. Biol. 17, 3629-3639. https://doi.org/10.1128/MCB.17.7.3629
  26. O'Donovan, T. R., O'Sullivan, G. C. and McKenna, S. L. (2011) Induction of autophagy by drug-resistant esophageal cancer cells promotes their survival and recovery following treatment with chemotherapeutics. Autophagy 7, 509-524. https://doi.org/10.4161/auto.7.5.15066
  27. Park, H. J., Lee, S. H., Son, D. J., Oh, K. W., Kim, K. H., Song, H. S., Kim, G. J., Oh, G. T., Yoon, D. Y. and Hong, J. T. (2004) Antiarthritic effect of bee venom: inhibition of inflammation mediator generation by suppression of NF-kappaB through interaction with the p50 subunit. Arthritis Rheum. 50, 3504-3515. https://doi.org/10.1002/art.20626
  28. Park, M. H., Choi, M. S., Kwak, D. H., Oh, K. W., Yoon do, Y., Han, S. B., Song, H. S., Song, M. J. and Hong, J. T. (2011) Anti-cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF-kappaB. Prostate 71, 801-812. https://doi.org/10.1002/pros.21296
  29. Park, M. H., Jo, M., Won, D., Song, H. S., Han, S. B., Song, M. J. and Hong, J. T. (2012a) Snake venom toxin from Vipera lebetina turanica induces apoptosis of colon cancer cells via upregulation of ROS- and JNK-mediated death receptor expression. BMC Cancer 12, 228. https://doi.org/10.1186/1471-2407-12-228
  30. Park, M. H., Son, D. J., Kwak, D. H., Song, H. S., Oh, K. W., Yoo, H. S., Lee, Y. M., Song, M. J. and Hong, J. T. (2009) Snake venom toxin inhibits cell growth through induction of apoptosis in neuroblastoma cells. Arch. Pharm. Res. 32, 1545-1554. https://doi.org/10.1007/s12272-009-2106-0
  31. Park, M. H., Song, M. J., Cho, M. C., Moon, D. C., Yoon do, Y., Han, S. B. and Hong, J. T. (2012b) Interleukin-32 enhances cytotoxic effect of natural killer cells to cancer cells via activation of death receptor 3. Immunology 135, 63-72. https://doi.org/10.1111/j.1365-2567.2011.03513.x
  32. Sancho-Martinez, I. and Martin-Villalba, A. (2009) Tyrosine phosphorylation and CD95: a FAScinating switch. Cell Cycle 8, 838-842. https://doi.org/10.4161/cc.8.6.7906
  33. Screpanti, V., Wallin, R. P., Grandien, A. and Ljunggren, H. G. (2005) Impact of FASL-induced apoptosis in the elimination of tumor cells by NK cells. Mol. Immunol. 42, 495-499. https://doi.org/10.1016/j.molimm.2004.07.033
  34. Smyth, M. J., Cretney, E., Takeda, K., Wiltrout, R. H., Sedger, L. M., Kayagaki, N., Yagita, H. and Okumura, K. (2001) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis. J. Exp. Med. 193, 661-670. https://doi.org/10.1084/jem.193.6.661
  35. Smyth, M. J., Hayakawa, Y., Takeda, K. and Yagita, H. (2002) New aspects of natural-killer-cell surveillance and therapy of cancer. Nat. Rev. Cancer 2, 850-861. https://doi.org/10.1038/nrc928
  36. Son, D. J., Park, M. H., Chae, S. J., Moon, S. O., Lee, J. W., Song, H. S., Moon, D. C., Kang, S. S., Kwon, Y. E. and Hong, J. T. (2007) Inhibitory effect of snake venom toxin from Vipera lebetina turanica on hormone-refractory human prostate cancer cell growth: induction of apoptosis through inactivation of nuclear factor kappaB. Mol. Cancer Ther. 6, 675-683.
  37. Song, J. K., Jo, M. R., Park, M. H., Song, H. S., An, B. J., Song, M. J., Han, S. B. and Hong, J. T. (2012) Cell growth inhibition and induction of apoptosis by snake venom toxin in ovarian cancer cell via inactivation of nuclear factor kappaB and signal transducer and activator of transcription 3. Arch. Pharm. Res. 35, 867-876. https://doi.org/10.1007/s12272-012-0512-1
  38. Sun, S. Y. (2011) Understanding the role of the death receptor 5/FADD/caspase-8 death signaling in cancer metastasis. Mol. Cell. Pharmacol. 3, 31-34.
  39. Tam, Y. K., Miyagawa, B., Ho, V. C. and Klingemann, H. G. (1999) Immunotherapy of malignant melanoma in a SCID mouse model using the highly cytotoxic natural killer cell line NK-92. J. Hematother. 8, 281-290. https://doi.org/10.1089/106161299320316
  40. Triller, N., Korosec, P., Kern, I., Kosnik, M. and Debeljak, A. (2006) Multidrug resistance in small cell lung cancer: expression of P-glycoprotein, multidrug resistance protein 1 and lung resistance protein in chemo-naive patients and in relapsed disease. Lung Cancer 54, 235-240. https://doi.org/10.1016/j.lungcan.2006.06.019
  41. Yasumura, S., Amoscato, A., Hirabayashi, H., Lin, W. C. and Whiteside, T. L. (1994) Proliferation of hematopoietic cell lines induced by a soluble factor derived from human squamous cell carcinomas of the head and neck. Cancer Immunol. Immunother. 39, 407-415. https://doi.org/10.1007/BF01534429
  42. Yoshida, T., Horinaka, M. and Sakai, T. (2010) "Combination-oriented molecular-targeting prevention" of cancer: a model involving the combination of TRAIL and a DR5 inducer. Environ. Health Prev. Med. 15, 203-210. https://doi.org/10.1007/s12199-009-0128-3
  43. Zhang, H. P., Takayama, K., Su, B., Jiao, X. D., Li, R. and Wang, J. J. (2011) Effect of sunitinib combined with ionizing radiation on endothelial cells. J. Radiat. Res. 52, 1-8. https://doi.org/10.1269/jrr.10013

Cited by

  1. Snake Venom-enhanced Cytotoxic Effect of Natural Killer Cells on A549 Human Lung Cancer Cell Growth vol.32, pp.1, 2015, https://doi.org/10.13045/acupunct.2015007
  2. Cobra venom cytotoxins; apoptotic or necrotic agents? vol.108, 2015, https://doi.org/10.1016/j.toxicon.2015.09.017
  3. Russell's viper venom affects regulation of small GTPases and causes nuclear damage vol.108, 2015, https://doi.org/10.1016/j.toxicon.2015.10.011
  4. Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells vol.2016, 2016, https://doi.org/10.1155/2016/1574971
  5. Biochemistry and pharmacology of proteins and peptides purified from the venoms of the snakes Macrovipera lebetina subspecies vol.158, pp.None, 2014, https://doi.org/10.1016/j.toxicon.2018.11.294
  6. The anti-cancer effect of Echis coloratus and Walterinnesia aegyptia venoms on colon cancer cells vol.40, pp.3, 2014, https://doi.org/10.1080/15569543.2018.1564774