PMID- 25025927 OWN - NLM STAT- MEDLINE DCOM- 20141009 LR - 20140818 IS - 1872-7980 (Electronic) IS - 0304-3835 (Linking) VI - 352 IP - 2 DP - 2014 Oct 1 TI - The ERK/eIF4F/Bcl-XL pathway mediates SGP-2 induced osteosarcoma cells apoptosis in vitro and in vivo. PG - 203-13 LID - S0304-3835(14)00331-0 [pii] LID - 10.1016/j.canlet.2014.06.015 [doi] AB - The aim of this study is to assess the molecular foundation of anti-tumor activity of SGP-2 in osteosarcoma cells. SGP-2 significantly blocks cell proliferation in human osteosarcoma U2OS cell model and inhibits tumor growth without causing apparent toxicity effect in mouse sarcoma S-180 cell-derived tumor model. Moreover, SGP-2 induces intrinsic apoptosis including the activation of caspase-3/7/9, the loss of mitochondrial transmembrane potential (DeltaPsim), and the release of cytochrome c from mitochondrion, controlled by the down-regulation of B-cell lymphoma-extra large (Bcl-XL). Further research reveals that SGP-2 inhibits the assembly of eukaryotic initiation factor 4F (eIF4F) complex which is responsible for the decline of Bcl-XL. Finally, extracellular-signal-regulated kinase (ERK) controls SGP-2 induced intrinsic apoptosis. Taken together, SGP-2 exerts anti-tumor effect through intrinsic apoptotic pathway controlled by ERK/eIF4F/Bcl-XL pathway. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Zhang, Zhenzhen AU - Zhang Z AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China. FAU - Zheng, Ying AU - Zheng Y AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China. FAU - Zhu, Rui AU - Zhu R AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China. FAU - Zhu, Yiqing AU - Zhu Y AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China. FAU - Yao, Wenbing AU - Yao W AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China. FAU - Liu, Wei AU - Liu W AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China; Department of Food Quality and Safety, China Pharmaceutical University, Jiangsu, China. FAU - Gao, Xiangdong AU - Gao X AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140712 PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (BCL2L1 protein, human) RN - 0 (Eukaryotic Initiation Factor-4F) RN - 0 (Polysaccharides) RN - 0 (bcl-X Protein) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 3.4.22.- (Caspases) SB - IM MH - Animals MH - Antineoplastic Agents, Phytogenic/*pharmacology/toxicity MH - Apoptosis/*drug effects MH - Bone Neoplasms/*drug therapy/genetics/metabolism/pathology MH - Caspases/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Dose-Response Relationship, Drug MH - Enzyme Activation MH - Eukaryotic Initiation Factor-4F/genetics/*metabolism MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Humans MH - Male MH - Membrane Potential, Mitochondrial/drug effects MH - Mice MH - Mice, Inbred ICR MH - Osteosarcoma/*drug therapy/genetics/metabolism/pathology MH - Polysaccharides/*pharmacology/toxicity MH - RNA Interference MH - Signal Transduction/drug effects MH - Time Factors MH - Transfection MH - Tumor Burden/drug effects MH - bcl-X Protein/genetics/*metabolism OTO - NOTNLM OT - Apoptosis OT - ERK OT - Osteosarcoma OT - eIF4F EDAT- 2014/07/16 06:00 MHDA- 2014/10/10 06:00 CRDT- 2014/07/16 06:00 PHST- 2014/04/16 00:00 [received] PHST- 2014/06/16 00:00 [revised] PHST- 2014/06/24 00:00 [accepted] PHST- 2014/07/16 06:00 [entrez] PHST- 2014/07/16 06:00 [pubmed] PHST- 2014/10/10 06:00 [medline] AID - S0304-3835(14)00331-0 [pii] AID - 10.1016/j.canlet.2014.06.015 [doi] PST - ppublish SO - Cancer Lett. 2014 Oct 1;352(2):203-13. doi: 10.1016/j.canlet.2014.06.015. Epub 2014 Jul 12.