PMID- 22020376 OWN - NLM STAT- MEDLINE DCOM- 20120503 LR - 20131121 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 26 IP - 1 DP - 2012 Feb TI - DEDC, a new flavonoid induces apoptosis via a ROS-dependent mechanism in human neuroblastoma SH-SY5Y cells. PG - 16-23 LID - 10.1016/j.tiv.2011.10.002 [doi] AB - The poor prognosis of neuroblastoma and lack of effective remedies have necessitated the application of new therapeutic scheme. Over the past few years, it has been found that flavonoids could exert specific cytotoxic activity towards cancer cells. 2-(cis-1,2-dihydroxy-4-oxo-cyclohex-5-enyl)-5,7-dihydroxy-chromone (DEDC) is a plant-derived flavonoid extracted from the aerial part of Macrothelypteris torresiana. The present study investigated the cytotoxic effects and underlying biochemical pathway leading to cell death on the response of DEDC treatment in human neuroblastoma cells. Our results indicated that (a) DEDC induced SH-SY5Y cells apoptosis by elevating reactive oxygen species (ROS) generation, and ROS generation that could be quenched by the antioxidants N-acetyl cystein (NAC). (b) The signal transducer and activator of transcription 3 (STAT3) played a crucial role in DEDC-triggered cell death. (c) Nuclear factor Kappa B (NF-kappaB) was activated following exposure to DEDC, and suppressing NF-kappaB pathway by pyrrolidine dithiocarbamate (PDTC, a potent NF-kappaB inhibitor) significantly increased neuroblastoma cell sensitivity to the pro-apoptotic effect of DEDC. Overall, this study shed light on the mechanism of action of DEDC and suggested more rational approaches to investigation and therapy for this childhood malignancy. CI - Crown Copyright (c) 2011. Published by Elsevier Ltd. All rights reserved. FAU - Liu, Huibin AU - Liu H AD - Key Laboratory of Natural Medicinal Chemistry and Resources Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan 430030, PR China. FAU - Jiang, Chunyang AU - Jiang C FAU - Xiong, Chaomei AU - Xiong C FAU - Ruan, Jinlan AU - Ruan J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111013 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (2-(cis-1,2-dihydroxy 4-oxo-cyclohex-5-enyl)-5,7-dihydroxychromone) RN - 0 (Antioxidants) RN - 0 (Cyclohexanones) RN - 0 (Flavones) RN - 0 (NF-kappa B) RN - 0 (Pyrrolidines) RN - 0 (Reactive Oxygen Species) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - 0 (Thiocarbamates) RN - 0 (Tumor Suppressor Protein p53) RN - 25769-03-3 (pyrrolidine dithiocarbamic acid) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/pharmacology MH - Antioxidants/pharmacology MH - Apoptosis/*drug effects MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Cyclohexanones/*pharmacology MH - Flavones/*pharmacology MH - Humans MH - NF-kappa B/antagonists & inhibitors/metabolism MH - Neuroblastoma/metabolism MH - Pyrrolidines/pharmacology MH - Reactive Oxygen Species/*metabolism MH - STAT3 Transcription Factor/metabolism MH - Signal Transduction/drug effects MH - Thiocarbamates/pharmacology MH - Tumor Suppressor Protein p53/metabolism EDAT- 2011/10/25 06:00 MHDA- 2012/05/04 06:00 CRDT- 2011/10/25 06:00 PHST- 2011/05/07 00:00 [received] PHST- 2011/07/28 00:00 [revised] PHST- 2011/10/05 00:00 [accepted] PHST- 2011/10/25 06:00 [entrez] PHST- 2011/10/25 06:00 [pubmed] PHST- 2012/05/04 06:00 [medline] AID - S0887-2333(11)00268-2 [pii] AID - 10.1016/j.tiv.2011.10.002 [doi] PST - ppublish SO - Toxicol In Vitro. 2012 Feb;26(1):16-23. doi: 10.1016/j.tiv.2011.10.002. Epub 2011 Oct 13.