Preferential involvement of mitochondria in Toll-like receptor 3 agonist-induced neuroblastoma cell apoptosis,but not in inhibition of cell growth |
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Authors: | Jiin-Haur Chuang Tsu-Kung Lin Ming-Hong Tai Chia-Wei Liou Sheng-Teng Huang Chia-Ling Wu Hung-Yi Lin Pei-Wen Wang |
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Institution: | (1) The Mitochondrial Research Unit, and the Division of Pediatric Surgery, Kaohsiung Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan;(2) The Mitochondrial Research Unit, and the Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan;(3) Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan;(4) The Mitochondrial Research Unit, and the Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan;(5) The Mitochondrial Research Unit, and the Department of Internal and Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Song, Kaohsiung 833, Taiwan; |
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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 (ρ0)-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. |
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