Fumonisin B1-induced apoptosis in neuroblastoma, glioblastoma and hypothalamic cell lines.
Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium verticilliodes, which commonly infects corn across the world. Fusarium fungi may also be found in moisture-damaged buildings. In this study, we investigated the role of apoptosis in the toxicity of FB(1) in four different cell lines. Activation of caspase-3-like protease, DNA fragmentation and expression of p53 and Bcl-2 family proteins were studied in mouse GT1-7 hypothalamic, rat C6 glioblastoma, human U-118MG glioblastoma, and human SH-SY5Y neuroblastoma cells exposed to 0.1-100microM FB(1) for 0-144h. Caspase-3-like protease activity increased in all cell lines, except SH-SY5Y, at 48-144h, and internucleosomal DNA fragmentation occurred in all of the cell lines, pointing to a role for apoptosis in the toxicity of FB(1). However, the expressions of p53 or pro- or antiapoptotic Bcl-2 family proteins (Bax, Bcl-2, Bcl-X(L) and Mcl-1) were not affected in any of the cell lines even after prolonged exposure to FB(1) at high doses. The results of this study, together with the results of our previous studies, provide evidence that FB(1) is a potential neurotoxin, but that the toxicity of FB(1) varies between different cell lines. The sensitivity of these cell lines towards FB(1) is as follows: U-118MG>GT1-7>C6>SH-SY5Y cells. These results are consistent with the assumption that cells of glial origin may be more sensitive towards FB(1) than cells of neural origin.
Stockmann-Juvala
Helene
H
Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, 00250 Helsinki, Finland. helene.stockmann-juvala@ttl.fi
Naarala
Jonne
J
Loikkanen
Jarkko
J
Vähäkangas
Kirsi
K
Savolainen
Kai
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D037341:Fumonisins / Q000633:toxicity*; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects* / Q000473:pathology; D009183:Mycotoxins / Q000633:toxicity*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D037341:Fumonisins; D009183:Mycotoxins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C056933:fumonisin B1; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases