title: CO(2) pneumoperitoneum induces in vitro hypoxic response culminating in apoptosis of human neuroblastoma cells.
abstract: The ablative role of minimally invasive surgery (MIS) in neuroblastoma (NB) is still controversial due to the possible CO₂ pneumoperitoneum side-effects on tumor aggressiveness. It is known that CO₂ produces hypoxic condition with changes in tumor microenvironment influencing cell functions. Here we investigated whether CO₂ exposure affects the transcription factor HIF-1α and the apoptotic signalling pathway in SH-SY5Y NB cells. SH-SY5Y cells were exposed to a pressure of 15 mmHg CO₂ (100%) for 4 h (T0) and then moved to normal condition for 24 h (T₂₄). In control and CO₂ -exposed cells, we analyzed the mRNA levels and DNA binding activity of HIF-1α. We also evaluated the proliferative activity and cell viability as well as caspase-9/3 cleavage and nuclear fragmentation. A significant increase in HIF- 1α activation was observed in SH-SY5Y cells exposed to CO₂ compared to control cells. CO₂ treatment also decreased the proliferation rate and the percentage of viable cells. In addition, the expression and cleavage of caspase-9 and -3 were significantly increased in NB cells exposed to CO₂. These data correlated with apoptotic feature observed in CO₂ -treated NB cells. Our findings show that CO₂ -induced hypoxic condition exerts cytotoxic effects on NB cells by eliciting mitochondrial apoptotic pathway and thereby improving the understanding of the possible clinical impact of CO₂ pneumoperitoneum on NB behaviour.
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Currò
authors.affiliation: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Italy.
authors.forename: A S
authors.initials: AS
authors.lastname: Montalto
authors.affiliation: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Impellizzeri
authors.affiliation: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Montalto
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Risitano
authors.affiliation: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Russo
authors.affiliation: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Perrone
authors.affiliation: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Chirico
authors.affiliation: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Arrigo
authors.affiliation: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Salpietro
authors.affiliation: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Romeo
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Ientile
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002245:Carbon Dioxide / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D011027:Pneumoperitoneum / Q000378:metabolism* / Q000473:pathology
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D002245:Carbon Dioxide; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9