title: The ERK/eIF4F/Bcl-XL pathway mediates SGP-2 induced osteosarcoma cells apoptosis in vitro and in vivo.
abstract: 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 (ΔΨm), 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.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Yao
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Jiangsu, China; School of Life Science and Technology, China Pharmaceutical University, Jiangsu, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D039562:Eukaryotic Initiation Factor-4F / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011134:Polysaccharides / Q000494:pharmacology* / Q000633:toxicity; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; D039562:Eukaryotic Initiation Factor-4F; D011134:Polysaccharides; D051020:bcl-X Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases
keywords: Apoptosis; ERK; Osteosarcoma; eIF4F