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Anticancer and Antiviral Activity of Chlorine Dioxide by Its Induction of the Reactive Oxygen Species

이산화염소의 활성산소 생성 유도에 의한 항암 및 항바이러스 활성

  • Kim, Yonggyun (Department of Bioresource Sciences, Andong National University) ;
  • Kumar, Sunil (Department of Bioresource Sciences, Andong National University) ;
  • Cheon, Wonsu (Department of Bioresource Sciences, Andong National University) ;
  • Eo, Hyunji (Department of Bioresource Sciences, Andong National University) ;
  • Kwon, Hyeok (Department of Life Sciences and Biotechnology, Korea University) ;
  • Jeon, Yongho (Department of Bioresource Sciences, Andong National University) ;
  • Jung, Jinboo (Department of Bioresource Sciences, Andong National University) ;
  • Kim, Wook (Department of Life Sciences and Biotechnology, Korea University)
  • Received : 2015.06.14
  • Accepted : 2015.11.04
  • Published : 2016.03.31

Abstract

Chlorine dioxide has been used for a disinfectant by exhibiting antimicrobial activity and is also potent to kill insect pests infesting stored grains. This study aimed to extend the usefulness of chlorine dioxide with respect to anticancer and antiviral activities. Cytotoxicity of chlorine dioxide was assessed against five different human cancer cell lines. Chlorine dioxide exhibited significant cytotoxicity against two breast cancer cell lines (MCF-7, MDA-MB-231) and three colorectal cancer cell lines (LoVo, HCT-116, SW-480). This cytotoxicity appeared to be associated with the capacity of chlorine dioxide to induce the production of reactive oxygen species (ROS). Compared to control insect cell lines, the cancer cell lines possessed much higher levels of ROS. On the other hand, a treatment of an antioxidant, vitamin E, significantly reduced the cytotoxicity, suggesting that the cytotoxicity was induced by high levels of ROS production. Chlorine dioxide exhibited antiviral activity against different viruses. A baculovirus, Autographa californica nuclear polyhedrosis virus (AcNPV), is a dsDNA insect virus and lost its viral activity to form polyhedral viral particles in response to chlorine dioxide. The antiviral activity against AcNPV was dependent on the incubation time with chlorine dioxide. Tobacco mosaic virus is a ssRNA plant virus and was reduced in its population after exposure to chlorine dioxide along with significant decrease of viral symptoms. These results indicate that chlorine dioxide possesses anticancer and antiviral activities probably due to its inducing activity of ROS production.

이산화염소는 높은 항생효과로 살균제로 사용되고 있고, 저곡해충을 대상으로 살충 효과도 보이고 있다. 본 연구는 이 이산화염소의 유용 효과를 넓히기 위해 이 물질이 항암 및 항바이러스 활성을 나타낼 수 있는 지를 검증하였다. 인체에 나타나는 5종의 암 세포주에 대해서 이산화염소의 세포독성을 분석하였다. 유방암 2종 세포주(MCF-7, MDA-MB-231)와 대장암 3종 세포주(LoVo, HCT-116, SW-480) 모두에 대해서 이산화염소는 높은 세포 독성을 나타냈다. 이러한 세포독성은 이산화염소의 활성산소 유발 효과에 기인된다. 이산화염소가 처리된 암세포주는 모두 세포내 높은 활성산소를 형성하였다. 이는 대조구로서 일반 곤충 세포주와 비교하여 훨씬 높은 활성산소를 지녔다. 반면에 항산화제인 비타민 E를 처리하면 이러한 세포독성이 크게 줄어 암 세포에 대해 높은 세포독성은 활성산소에 의해 기인되었다는 것을 입증하였다. 또한 이산화염소는 서로 다른 바이러스에 대해서 항바이러스 활성을 나타냈다. 곤충병원성 바이러스이고 이중 가닥의 DNA 게놈을 지닌 벡큘로바이러스의 일종인 Autographa californica nuclear polyhedrosis virus (AcNPV)는 이산화염소 노출에 따라 활성을 잃어 핵다각체 형성 능력이 크게 둔화되었다. AcNPV에 대한 이산화염소의 항바이러스 효과는 반응 시간에 비례하여 증가했다. 식물병원성 바이러스이고 단일가닥의 RNA 게놈을 지닌 담배모자이크바이러스는 이산화염소 노출에 따라 바이러스 함량이 줄었고, 담배에 대한 병원력도 낮아졌다. 따라서 본 연구는 이산화염소가 항암 및 항바이러스 활성을 지니며, 이는 이 물질에 의한 높은 활성산소 유발에 기인된 것으로 판명되었다.

Keywords

References

  1. Aung EE, Ueno M, Zaitsu T, Furukawa S, and Kawaguchi Y (2015) Effectiveness of three oral hygiene regimes on oral malodor reduction: a randomized clinical trial. Trials 16, 31. https://doi.org/10.1186/s13063-015-0549-9
  2. Bang J, Hing A, Kim H, Beuchat LR, Rhee MS, Kim Y et al. (2014) Inactivation of Escherichia coli O157:H7 in biofilm on food-contact surfaces by sequential treatments of aqueous chlorine dioxide and drying. Int J Food Microbiol 191, 129−34. https://doi.org/10.1016/j.ijfoodmicro.2014.09.014
  3. Choi B, Ryoo I, Kang HC, and Kwak M (2014) The sensitivity of cancer cells to pheophorbide a-based photodynamic therapy is enhanced by NRF2 silencing. PLoS One 9, e107158. https://doi.org/10.1371/journal.pone.0107158
  4. Clem RJ and Passarell AL (2013) Baculoviruses: sophisticated pathogens of insects. PLoS Pathog 9, e1003729. https://doi.org/10.1371/journal.ppat.1003729
  5. Don G (1998) The chlorine dioxide handbook. Am Water Works Assoc, 3−4.
  6. Gibbs SG, Lowe JJ, Smith PA, and Hewlett AL (2012) Gaseous chlorine dioxide as an alternative for bedbug control. Infect Control Hosp Epidemiol 33, 495−9. https://doi.org/10.1086/665320
  7. Gordon G and Rosenblatt AA (2005) Chlorine dioxide: the current state of the art. Ozone Sci Eng 27, 203−7. https://doi.org/10.1080/01919510590945741
  8. Hayes JD, McMahon M, Chowdhry S, and Dinkova-Kostova AT (2010) Cancer chemoprevention mechanisms mediated through the Keap1-Nrf2 pathway. Antioxid Redox Signal 13, 1713−48. https://doi.org/10.1089/ars.2010.3221
  9. Hinenoya A, Awasthi SP, Yasuda N, Shima A, Morino H, Koizumi T et al. (2015) Chlorine dioxide is a superior disinfectant against multi-drug resistant Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii. Jpn J Infect Dis, in press.
  10. Huang J, Wang L, Nanqi R, and Junli H (1997) Disinfection effect of chlorine dioxide on bacteria in water. Wat Res 31, 607−13. https://doi.org/10.1016/S0043-1354(96)00275-8
  11. Jeon YH, Kim JH, and Kim YH (2008) Involvement of heat-stable and proteinaceous materials in the culture of Pseudomonas putida JB-1 for the inhibition of tobacco mosaic virus infection. Plant Pathol. J. 24, 328−36. https://doi.org/10.5423/PPJ.2008.24.3.328
  12. Jin M, Shan J, Chen Z, Guo X, Shen Z, Qiu Z et al. (2013) Chlorine dioxide inactivation of enterovirus 71 in water and its impact on genomic targets. Environ Sci Technol 47, 4590−7. https://doi.org/10.1021/es305282g
  13. Jung S, Kwoen M, Choi JY, Je YH, and Kim Y (2006) Parasitism of Cotesia spp. enhances susceptibility of Plutella xylostella to other pathogens. J Asia Pac Entomol 9, 255−63. https://doi.org/10.1016/S1226-8615(08)60300-3
  14. Kumar S, Park J, Kim E, Na J, Chun YS, Kwon H et al. (2015) Oxidative stress induced by chlorine dioxide as an insecticidal factor to the Indian meal moth, Plodia interpunctella Pesti Biochem Physiol, in press.
  15. Nam H, Seo HS, Bang J, Kim H, Beuchat LR, and Ryu JH (2014) Efficacy of gaseous chlorine dioxide in inactivating Bacillus cereus attached to and in a biofilm on stainless steel. Int J Food Microbiol 188, 122−7. https://doi.org/10.1016/j.ijfoodmicro.2014.07.009
  16. Nishikiori R, Nomura Y, Sawajiri M, Masuki K, Hirata I, and Okazaki M (2008) Influence of chlorine dioxide on cell death and cell cycle of human gingival fibroblasts. J Dent 36, 993−8. https://doi.org/10.1016/j.jdent.2008.08.006
  17. Ogata N (2007) Denaturation of protein by chlorine dioxide: oxidative modification of tryptophan and tyrosine residues. Biochemistry 46, 4898−911. https://doi.org/10.1021/bi061827u
  18. Ogata N (2012) Inactivation of influenza virus haemagglutinin by chlorine dioxide: oxidation of the conserved tryptophan 153 residue in the receptor-binding site. J Gen Virol 93, 2558−68. https://doi.org/10.1099/vir.0.044263-0
  19. Sanekata T, Fukuda T, Miura T, Morino H, Lee C, Maeda K et al. (2010) Evaluation of the antiviral activity of chlorine dioxide and sodium hypochlorite against feline calicivirus, human influenza virus, measles virus, canine distemper virus, human herpesvirus, human adenovirus, canine adenovirus and canine parvovirus. Biocontrol Sci 15, 45−9. https://doi.org/10.4265/bio.15.45
  20. Scholthof KB (2004) Tobacco mosaic virus: a model system for plant biology. Annu Rev Phytopathol 42, 13−34. https://doi.org/10.1146/annurev.phyto.42.040803.140322
  21. Sullivan LB and Chandel NS (2014) Mitochondrial reactive oxygen species and cancer. Cancer Metab 2, 17. https://doi.org/10.1186/2049-3002-2-17
  22. Sun X, Bai J, Ference C, Wang Z, Zhang Y, Narciso J et al. (2014) Antimicrobial activity of controlled-release chlorine dioxide gas on fresh blueberries. J Food Prot 77, 1127−32. https://doi.org/10.4315/0362-028X.JFP-13-554
  23. Taneja S, Mishra N, and Malik S (2014) Comparative evaluation of human pulp tissue dissolution by different concentrations of chlorine dioxide, calcium hypochlorite and sodium hypochlorite: an in vitro study. J Conserv Dent 17, 541−5. https://doi.org/10.4103/0972-0707.144590
  24. Thimmulappa RK, Mai KH, Srisuma S, Kensler TW, and Yamamoto M (2002) Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res 62, 5196−203.
  25. Vlad S, Anderson WB, Peldszus S, and Huck PM (2014) Removal of the cyanotoxin-a by drinking water treatment processes: a review. J Water Health 12, 601−17. https://doi.org/10.2166/wh.2014.018
  26. Volk CJ, Hofmann R, Chauret C, Gagnom GA, Ranger G, and Andrews RC (2002) Implementation of chlorine dioxide disinfection: effects of the treatment change on drinking water quality in a full-scale distribution system. J Environ Eng Sci 1, 323−30. https://doi.org/10.1139/s02-026
  27. Wu YF, Cao R, Wei NS, and Zhou GH (1995) Screening and application of biological pesticides virus. World Agr 5, 35−6.
  28. Yang W, Zou L, Huang C, and Lei Y (2014) Redox regulation of cancer metastasis: molecular signaling and therapeutic opportunities. Drug Dev Res 75, 331−41. https://doi.org/10.1002/ddr.21216

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