Browse > Article
http://dx.doi.org/10.7314/APJCP.2016.17.S3.299

Apoptotic Effects of the B Subunit of Bacterial Cytolethal Distending Toxin on the A549 Lung Cancer Cell Line  

Yaghoobi, Hajar (Department of Biotechnology, School of Medicine, Shahid Beheshti University of Medical Sciences)
Bandehpour, Mojgan (Department of Biotechnology, School of Medicine, Shahid Beheshti University of Medical Sciences)
Kazemi, Bahram (Department of Biotechnology, School of Medicine, Shahid Beheshti University of Medical Sciences)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.17, no.sup3, 2016 , pp. 299-304 More about this Journal
Abstract
Cytolethal distending toxin (CDT) is a secreted tripartite genotoxin produced by many pathogenic gram-negative bacteria. It is composed of three subunits, CdtA, CdtB and CdtC, and CdtB-associated deoxyribonuclease (DNase) activity is essential for the CDT toxicity. In the present study, to design a novel potentially antitumor drug against lung cancer, the possible mechanisms of cdtB anticancer properties were explored in the A549 human lung adenocarcinoma cell line. A recombinant plasmid pcDNA3.1/cdtB was constructed expressing CdtB of human periodontal bacterium Aggregatibacter actinomycetemcomitans and investigated for toxic properties in A549 cells and possible mechanisms. It was observed that plasmid pcDNA3.1/cdtB caused loss of cell viability, morphologic changes and induction of apoptosis. Furthermore, measurement of caspase activity indicated involvement of an intrinsic pathway of cell apoptosis. Consequently, the recombinant plasmid pcDNA3.1/cdtB may have potential as a new class of therapeutic agent for gene therapy of lung cancer.
Keywords
Cytolethal distending toxin; genotoxin; recombinant plasmid; Aggregatibacter actinomycetemcomitans;
Citations & Related Records
Times Cited By KSCI : 5  (Citation Analysis)
연도 인용수 순위
1 Bandala C, Perez-Santos JL, Lara-Padilla E, et al (2013). Effect of botulinum toxin a on proliferation and apoptosis in the t47d breast cancer cell line. Asian Pac J Cancer Prev, 14, 891-4.   DOI
2 Bermudes D, Zheng LM ,King IC (2002). Live bacteria as anticancer agents and tumor-selective protein delivery vectors. Curr Opin Drug Discov Devel, 5, 194-9.
3 Bezine E, Vignard J ,Mirey G (2014). The cytolethal distending toxin effects on mammalian cells: A DNA damage perspective. Cells, 3, 592-615.   DOI
4 Engedal N, Skotland T, Torgersen ML, et al (2011). Shiga toxin and its use in targeted cancer therapy and imaging. Microb Biotechnol, 4, 32-46.   DOI
5 Frankel AE, Rossi P, Kuzel TM, et al (2002). Diphtheria fusion protein therapy of chemoresistant malignancies. Curr Cancer Drug Targets, 2, 19-36.   DOI
6 Govindan R, Page N, Morgensztern D, et al (2006). Changing epidemiology of small-cell lung cancer in the united states over the last 30 years: Analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol, 24, 4539-44.   DOI
7 Hough CD, Sherman-Baust CA, Pizer ES, et al (2000). Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. Cancer Res, 60, 6281-7.
8 Kominsky SL, Vali M, Korz D, et al (2004). Clostridium perfringens enterotoxin elicits rapid and specific cytolysis of breast carcinoma cells mediated through tight junction proteins claudin 3 and 4. Am J Pathol, 164, 1627-33.   DOI
9 Lai CK, Lu YL, Hsieh JT, et al (2014). Development of chitosan/heparin nanoparticle-encapsulated cytolethal distending toxin for gastric cancer therapy. Nanomedicine (Lond), 9, 803-17.   DOI
10 Liu CC, Yang H, Zhang LL, et al (2014). Biotoxins for cancer therapy. Asian Pac J Cancer Prev, 15, 4753-8.   DOI
11 Michl P, Buchholz M, Rolke M, et al (2001). Claudin-4: A new target for pancreatic cancer treatment using clostridium perfringens enterotoxin. Gastroenterology, 121, 678-84.   DOI
12 Patyar S, Joshi R, Byrav DS, et al (2010). Bacteria in cancer therapy: A novel experimental strategy. J Biomed Sci, 17, 21.   DOI
13 Mizrahi A, Hochberg A, Amiur S, et al (2010). Targeting diphtheria toxin and tnf alpha expression in ovarian tumors using the h19 regulatory sequences. Int J Clin Exp Med, 3, 270-82.
14 Nishihara T ,Koseki T (2004). Microbial etiology of periodontitis. Periodontol 2000, 36, 14-26.   DOI
15 Pastan I (1997). Targeted therapy of cancer with recombinant immunotoxins. Biochim Biophys Acta, 1333, 1-6.
16 Qiu Y, Peng GL, Liu QC, et al (2012). Selective killing of lung cancer cells using carcinoembryonic antigen promoter and double suicide genes, thymidine kinase and cytosine deaminase (pcea-tk/cd). Cancer Lett, 316, 31-8.   DOI
17 Saiki K, Konishi K, Gomi T, et al (2001). Reconstitution and purification of cytolethal distending toxin of actinobacillus actinomycetemcomitans. Microbiol Immunol, 45, 497-506.   DOI
18 Sargent JM ,Taylor CG (1989). Appraisal of the mtt assay as a rapid test of chemosensitivity in acute myeloid leukaemia. Br J Cancer, 60, 206-10.   DOI
19 Sun S, Schiller JH, Spinola M, et al (2007). New molecularly targeted therapies for lung cancer. J Clin Invest, 117, 2740-50.   DOI
20 Wang S, Shu JZ, Cai Y, et al (2012). Establishment and characterization of mtdh knockdown by artificial microrna interference - functions as a potential tumor suppressor in breast cancer. Asian Pac J Cancer Prev, 13, 2813-8.   DOI
21 Wising C, Magnusson M, Ahlman K, et al (2010). Toxic activity of the cdtb component of haemophilus ducreyi cytolethal distending toxin expressed from an adenovirus 5 vector. Apmis, 118, 143-9.   DOI
22 Zhou W, Wang J, Man WY, et al (2015). Sirna silencing ezh2 reverses cisplatin-resistance of human non-small cell lung and gastric cancer cells. Asian Pac J Cancer Prev, 16, 2425-30.   DOI
23 Yamamoto K, Tominaga K, Sukedai M, et al (2004). Delivery of cytolethal distending toxin b induces cell cycle arrest and apoptosis in gingival squamous cell carcinoma in vitro. Eur J Oral Sci, 112, 445-51.   DOI
24 Yildirim F, Baha A, Yurdakul AS, et al (2015). Comparison of single agent gemcitabine and docetaxel in second-line therapy for advanced stage non-small cell lung cancer in a university hospital in turkey. Asian Pac J Cancer Prev, 16, 7859-65.   DOI