PMID- 32975211 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20240204 IS - 0219-1032 (Electronic) IS - 1016-8478 (Print) IS - 1016-8478 (Linking) VI - 43 IP - 9 DP - 2020 Sep 30 TI - Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species. PG - 813-820 LID - 10.14348/molcells.2020.2234 [doi] AB - NB4 cell, the human acute promyelocytic leukemia (APL) cell line, was treated with various concentrations of arsenic trioxide (ATO) to induce apoptosis, measured by staining with 7-amino-actinomycin D (7-AAD) by flow cytometry. 2', 7'-dichlorodihydro-fluorescein-diacetate (DCF-DA) and MitoSOX(TM) Red mitochondrial superoxide indicator were used to detect intracellular and mitochondrial reactive oxygen species (ROS). The steady-state level of SO(2) (Cysteine sulfinic acid, Cys-SO(2)H) form for peroxiredoxin 3 (PRX3) was measured by a western blot. To evaluate the effect of sulfiredoxin 1 depletion, NB4 cells were transfected with small interfering RNA and analyzed for their influence on ROS, redox enzymes, and apoptosis. The mitochondrial ROS of NB4 cells significantly increased after ATO treatment. NB4 cell apoptosis after ATO treatment increased in a time-dependent manner. Increased SO(2) form and dimeric PRX3 were observed as a hyperoxidation reaction in NB4 cells post-ATO treatment, in concordance with mitochondrial ROS accumulation. Sulfiredoxin 1 expression is downregulated by small interfering RNA transfection, which potentiated mitochondrial ROS generation and cell growth arrest in ATO-treated NB4 cells. Our results indicate that ATO-induced ROS generation in APL cell mitochondria is attributable to PRX3 hyperoxidation as well as dimerized PRX3 accumulation, subsequently triggering apoptosis. The downregulation of sulfiredoxin 1 could amplify apoptosis in ATO-treated APL cells. FAU - Mun, Yeung-Chul AU - Mun YC AUID- ORCID: 0000-0002-1882-3983 AD - Department of Hematology and Oncology, Ewha Womans University College of Medicine, Seoul 07985, Korea. FAU - Ahn, Jee Young AU - Ahn JY AUID- ORCID: 0000-0002-9813-0481 AD - Department of Hematology and Oncology, Ewha Womans University College of Medicine, Seoul 07985, Korea. FAU - Yoo, Eun Sun AU - Yoo ES AUID- ORCID: 0000-0001-6419-2337 AD - Department of Pediatrics, Ewha Womans University College of Medicine, Seoul 07985, Korea. FAU - Lee, Kyoung Eun AU - Lee KE AUID- ORCID: 0000-0003-1596-8666 AD - Department of Hematology and Oncology, Ewha Womans University College of Medicine, Seoul 07985, Korea. FAU - Nam, Eun Mi AU - Nam EM AUID- ORCID: 0000-0003-0108-5352 AD - Department of Hematology and Oncology, Ewha Womans University College of Medicine, Seoul 07985, Korea. FAU - Huh, Jungwon AU - Huh J AUID- ORCID: 0000-0001-8758-9847 AD - Department of Laboratory Medicine, Ewha Womans University College of Medicine, Seoul 07985, Korea. FAU - Woo, Hyun Ae AU - Woo HA AUID- ORCID: 0000-0002-3483-1203 AD - Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea. FAU - Rhee, Sue Goo AU - Rhee SG AUID- ORCID: 0000-0002-4740-4956 AD - Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea. FAU - Seong, Chu Myong AU - Seong CM AUID- ORCID: 0000-0001-9985-9218 AD - Department of Hematology and Oncology, Ewha Womans University College of Medicine, Seoul 07985, Korea. LA - eng PT - Journal Article PL - United States TA - Mol Cells JT - Molecules and cells JID - 9610936 RN - 0 (Antineoplastic Agents) RN - 0 (Reactive Oxygen Species) RN - EC 1.11.1.15 (Peroxiredoxin III) RN - S7V92P67HO (Arsenic Trioxide) SB - IM MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/drug effects MH - Arsenic Trioxide/*pharmacology MH - Cell Line, Tumor MH - Humans MH - Leukemia, Promyelocytic, Acute/*drug therapy/metabolism/pathology MH - Mitochondria/*metabolism MH - Peroxiredoxin III/*metabolism MH - Reactive Oxygen Species/metabolism MH - Transfection PMC - PMC7528683 OTO - NOTNLM OT - acute promyelocytic leukemia OT - arsenic trioxide OT - peroxiredoxin 3 COIS- CONFLICT OF INTEREST The authors have no potential conflicts of interest to disclose. EDAT- 2020/09/26 06:00 MHDA- 2021/06/25 06:00 PMCR- 2020/09/30 CRDT- 2020/09/25 08:36 PHST- 2019/10/15 00:00 [received] PHST- 2020/08/24 00:00 [revised] PHST- 2020/08/25 00:00 [accepted] PHST- 2020/09/25 08:36 [entrez] PHST- 2020/09/26 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/09/30 00:00 [pmc-release] AID - S1016-8478(23)00343-6 [pii] AID - molce-43-813 [pii] AID - 10.14348/molcells.2020.2234 [doi] PST - ppublish SO - Mol Cells. 2020 Sep 30;43(9):813-820. doi: 10.14348/molcells.2020.2234.