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: Zhenzhen Zhang, Ying Zheng, Rui Zhu, Yiqing Zhu, Wenbing Yao, Wei Liu, Xiangdong Gao
• Journal: Cancer letters (Cancer Lett) Vol. 352 Issue 2 Pg. 203-13 (Oct 01 2014) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 25025927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• BCL2L1 protein, human
• Eukaryotic Initiation Factor-4F
• Polysaccharides
• bcl-X Protein
• Extracellular Signal-Regulated MAP Kinases
• Caspases

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology, toxicity)
• Apoptosis (drug effects)
• Bone Neoplasms (drug therapy, genetics, metabolism, pathology)
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Enzyme Activation
• Eukaryotic Initiation Factor-4F (genetics, metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Mice, Inbred ICR
• Osteosarcoma (drug therapy, genetics, metabolism, pathology)
• Polysaccharides (pharmacology, toxicity)
• RNA Interference
• Signal Transduction (drug effects)
• Time Factors
• Transfection
• Tumor Burden (drug effects)
• bcl-X Protein (genetics, metabolism)