이산화염소의 활성산소 생성 유도에 의한 항암 및 항바이러스 활성 = Original Article: Soil/Pesticidal/Environmental Sciences : Anticancer and Antiviral Activity of Chlorine Dioxide by Its Induction of the Reactive Oxygen Species

다국어 초록 (Multilingual 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 ass℃iated 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.

참고문헌 (Reference)

1 김성무, "소화기 영역에서 Epithelial-mesenchymal Transition의 역할" 대한소화기학회 56 (56): 69-77, 2010

2 Virtakoivu R, "Vimentin-ERK Signaling Uncouples Slug Gene Regulatory Function" 75 : 2349-2362, 2015

3 Scholthof KB, "Tobacco mosaic virus: a model system for plant biology" 42 : 13-34, 2004

4 Choi B, "The sensitivity of cancer cells to pheophorbide a-based photodynamic therapy is enhanced by NRF2silencing" 9 : e107158-, 2014

5 Don G, "The chlorine dioxide handbook"

6 Wu YF, "Screening and application of biological pesticides virus" 5 : 35-36, 1995

7 Vlad S, "Removal of the cyanotoxin-a by drinking water treatment processes: a review" 12 : 601-617, 2014

8 Yang W, "Redox regulation of cancer metastasis: molecular signaling and therapeutic opportunities" 75 : 331-341, 2014

9 Novo E, "Redox mechanisms in hepatic chronic wound healing and fibrogenesis" 1 : 5-, 2008

10 정성채, "Parasitism of Cotesia spp. Enhances Susceptibility of Plutella xylostella to Other Pathogens" 한국응용곤충학회 9 (9): 255-263, 2006

11 Kumar S, "Oxidative stress induced by chlorine dioxide as an insecticidal factor to the Indian meal moth" 2015

12 Hiraga R, "Nox4-derived ROS signaling contributes to TGF-beta-induced epithelial-mesenchymal transition in pancreatic cancer cells" 33 : 4431-4438, 2013

13 Boudreau HE, "Nox4 involvement in TGF-beta and SMAD3-driven induction of the epithelial-to-mesenchymal transition and migration of breast epithelial cells" 53 : 1489-1499, 2012

14 Serrander L, "NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation" 406 : 105-114, 2007

15 De Minicis S, "NOX in liver fibrosis" 462 : 266-272, 2007

16 Jiang F, "NADPH oxidasedependent redox signaling in TGF-beta-mediated fibrotic responses" 2 : 267-272, 2014

17 Sullivan LB, "Mitochondrial reactive oxygen species and cancer" 2 : 17-, 2014

18 Zhang M, "Liver myofibroblasts from hepatitis B related liver failure patients may regulate natural killer cell function via PGE2" 12 : 308-, 2014

19 전용호, "Involvement of Heat-stable and Proteinaceous Materials in the Culture of Pseudomonas putida JB-1 for the Inhibition of Tobacco mosaic virus Infection" 한국식물병리학회 24 (24): 328-336, 2008

20 Nishikiori R, "Influence of chlorine dioxide on cell death and cell cycle of human gingival fibroblasts" 36 : 993-998, 2008

21 Ogata N, "Inactivation of influenza virus haemagglutinin by chlorine dioxide: oxidation of the conserved tryptophan 153 residue in the receptor-binding site" 93 : 2558-2568, 2012

22 Bang J, "Inactivation of Escherichia coli O157:H7 in biofilm on food-contact surfaces by sequential treatments of aqueous chlorine dioxide and drying" 191 : 129-134, 2014

23 Volk CJ, "Implementation of chlorine dioxide disinfection: effects of the treatment change on drinking water quality in a full-scale distribution system" 1 : 323-330, 2002

24 Thimmulappa RK, "Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray" 62 : 5196-5203, 2002

25 Shepard CW, "Hepatitis B virus infection: epidemiology and vaccination" 28 : 112-125, 2006

26 Guo GH, "Hepatitis B virus X protein promotes proliferation and upregulates TGF-beta1 and CTGF in human hepatic stellate cell line, LX-2" 8 : 59-64, 2009

27 Albanis E, "Hepatic fibrosis. Pathogenesis and principles of therapy" 5 : 315-334, 2001

28 Ha HL, "HBx-induced reactive oxygen species activates hepatocellular carcinogenesis via dysregulation of PTEN/Akt pathway" 16 : 4932-4937, 2010

29 Gibbs SG, "Gaseous chlorine dioxide as an alternative for bedbug control" 33 : 495-499, 2012

30 Sanekata T, "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" 15 : 45-49, 2010

31 Nam H, "Efficacy of gaseous chlorine dioxide in inactivating Bacillus cereus attached to and in a biofilm on stainless steel" 188 : 122-127, 2014

32 Aung EE, "Effectiveness of three oral hygiene regimes on oral malodor reduction: a randomized clinical trial" 16 : 31-, 2015

33 Huang J, "Disinfection effect of chlorine dioxide on bacteria in water" 31 : 607-613, 1997

34 Ogata N, "Denaturation of protein by chlorine dioxide: oxidative modification of tryptophan and tyrosine residues" 46 : 4898-4911, 2007

35 Taneja S, "Comparative evaluation of human pulp tissue dissolution by different concentrations of chlorine dioxide, calcium hypochlorite and sodium hypochlorite: an in vitro study" 17 : 541-545, 2014

36 남현자, "Co-treatment with hepatocyte growth factor and TGF-β1 enhances migration of HaCaT cells through NADPH oxidase-dependent ROS generation" 생화학분자생물학회 42 (42): 270-279, 2010

37 Vassiliadis E, "Circulating levels of citrullinated and MMPdegraded vimentin(VICM)in liver fibrosis related pathology" 4 : 403-414, 2012

38 Gordon G, "Chlorine dioxide: the current state of the art" 27 : 203-207, 2005

39 Hinenoya A, "Chlorine dioxide is a superior disinfectant against multi-drug resistant Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii" 2015

40 Jin M, "Chlorine dioxide inactivation of enterovirus 71 in water and its impact on genomic targets" 47 : 4590-4597, 2013

41 Hayes JD, "Cancer chemoprevention mechanisms mediated through the Keap1-Nrf2pathway" 13 : 1713-1748, 2010

42 Clem RJ, "Baculoviruses : sophisticated pathogens of insects" 9 : e1003729-, 2013

43 Sun X, "Antimicrobial activity of controlled-release chlorine dioxide gas on fresh blueberries" 77 : 1127-1132, 2014

44 Kim YM, "Activation of NADPH oxidase subunit NCF4induces ROS-mediated EMT signaling in HeLa cells" 26 : 784-796, 2014

45 Chang Hee Yang, "A Natural Mutation of the Hepatitis B Virus X Gene Affects Cell Cycle Progression and Apoptosis in Huh7 Cells" 한국응용생명화학회 55 (55): 229-236, 2012