Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10899752 | Cancer Letters | 2014 | 11 Pages |
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 (ÎΨm), 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.
Keywords
MMPCFDA-seeIF4F4E-BP1Bcl-xLΔΨm12-O-tetradecanoylphorbol-13-acetateERKtPA5-FU5-bromo-2′-deoxyuridine7-methylguanosineDMSOOsteosarcomaCSABrdUApoptosisDimethyl sulfoxideCyclosporine A5-fluorouracilB-cell lymphoma-extra largeMitochondrial membrane permeabilizationMitochondrial transmembrane potentialextracellular-signal-regulated kinase
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Authors
Zhenzhen Zhang, Ying Zheng, Rui Zhu, Yiqing Zhu, Wenbing Yao, Wei Liu, Xiangdong Gao,