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Title: The ERK/eIF4F/Bcl-XL pathway mediates SGP-2 induced osteosarcoma cells apoptosis in vitro and in vivo. Author: Zhang Z, Zheng Y, Zhu R, Zhu Y, Yao W, Liu W, Gao X. Journal: Cancer Lett; 2014 Oct 01; 352(2):203-13. PubMed ID: 25025927. 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.[Abstract] [Full Text] [Related] [New Search]