title: Preferential involvement of mitochondria in Toll-like receptor 3 agonist-induced neuroblastoma cell apoptosis, but not in inhibition of cell growth.
abstract: Double-stranded RNA (dsRNA) can mediate its therapeutic effect through Toll-like receptor 3 (TLR3) expressed on tumor cells including neuroblastoma. We used synthetic dsRNA polyinosinic-polycytidylic acid [Poly(I:C)] as a TLR3 agonist to treat TLR3-expressing SK-N-AS neuroblatoma (NB) cells. We found up-regulation of endoplasmic reticulum (ER) stress proteins glucose-regulated protein 78 and inositol-requiring enzyme 1. Bafilomycin A1, an inhibitor of ER function, effectively blocked poly(I:C)-induced activation of caspase-8, -9, and -3, MnSOD and glutathione peroxidase 1 and reduced poly(I:C)-induced SK-N-AS apoptosis. Pan caspase inhibitor and inhibitor of caspase-9, but not of caspase-8, inhibited poly(I:C)-induced activated caspase-3 expression. Rho zero (ρ(0))-SK-N-AS cells were resistant to poly(I:C)-induced mitochondrial reactive oxygen species production and apoptosis, but not to inhibition of cell growth, as compared to parent SK-N-AS cells. Taking together, these findings suggest that mitochondria are preferentially involved in poly(I:C)-induced NB cell apoptosis, but not in inhibition of cell growth. A crosstalk between mitochondria and ER is implicated.
authors.affiliation: The Mitochondrial Research Unit, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan.
authors.forename: Jiin-Haur
authors.initials: JH
authors.lastname: Chuang
authors.forename: Tsu-Kung
authors.initials: TK
authors.lastname: Lin
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Liou
authors.forename: Sheng-Teng
authors.initials: ST
authors.lastname: Huang
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Wu
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Lin
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011070:Poly I-C / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D051196:Toll-Like Receptor 3; D011070:Poly I-C