title: A mitochondria-mediated apoptotic pathway induced by deoxynivalenol in human colon cancer cells.
abstract: Deoxynivalenol (DON), known colloquially as "vomitoxin", is a pathogenic mycotoxin produced by Fusarium fungi. Human food poisoning outbreaks, with nausea, diarrhea, and vomiting as primary symptoms, have been associated with Fusarium-infected cereals. Therefore, this study was designed to determine the molecular aspects of DON in human colon cancer cells (HT-29). To this aim, we have monitored the effects of DON on (i) cellular morphological changes via optical and transmission electron microscopy, especially in regards to cell viability and mitochondria changes, and (ii) its effects on key regulators of cell apoptosis, including cytochrome c, caspase-9, caspase-3, Bcl-2, Bax, and Bid. Our results showed that DON treatment inhibited cell proliferation, induced significant morphological changes, and promoted the activation of cytochrome c and caspases. Furthermore, changes in Bcl-2, Bax, and Bid expression were detected. The relative expression profile of Bcl-2 was contrary to that of Bax and Bid, as Bcl-2 expression decreased as the concentrations DON increased, reaching a minimum at the highest concentration of DON. We concluded that DON-induced apoptosis was caused by mitochondrial dysfunction and subsequent release of cytochrome c into the cytoplasm and successive activation of caspases, and this was likely regulated by Bcl-2 family proteins.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. mayena@163.com
authors.forename: Yanna
authors.initials: Y
authors.lastname: Ma
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Shi
authors.forename: Chenghua
authors.initials: C
authors.lastname: He
authors.forename: Jujing
authors.initials: J
authors.lastname: Ding
authors.forename: Xichun
authors.initials: X
authors.lastname: Wang
authors.forename: Jifei
authors.initials: J
authors.lastname: Ma
authors.forename: Haibin
authors.initials: H
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D014255:Trichothecenes / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D014255:Trichothecenes; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D020169:Caspases; C007262:deoxynivalenol