title: Apoptotic Effects of the B Subunit of Bacterial Cytolethal Distending Toxin on the A549 Lung Cancer Cell Line.
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.
authors.affiliation: Department of Biotechnology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran E-mail: Bandehpour@gmail.com.
authors.forename: Hajar
authors.initials: H
authors.lastname: Yaghoobi
authors.forename: Mojgan
authors.initials: M
authors.lastname: Bandehpour
authors.forename: Bahram
authors.initials: B
authors.lastname: Kazemi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016976:Aggregatibacter actinomycetemcomitans / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001427:Bacterial Toxins / Q000494:pharmacology*; D015153:Blotting, Western; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D001427:Bacterial Toxins; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; C067044:cytolethal distending toxin; D020169:Caspases