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Dolichol‐linked oligosaccharide synthesis inhibitor reduces the survival potential of capillary endothelial cells
Author(s) -
Banerjee Aditi,
Miller Meriandrys,
Baksi Krishna,
Banerjee Dipak K
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.693.9
Subject(s) - tunicamycin , angiogenesis , protein kinase b , microbiology and biotechnology , chemistry , dolichol , vascular endothelial growth factor , phosphorylation , endothelial stem cell , cancer research , apoptosis , biology , unfolded protein response , biochemistry , biosynthesis , vegf receptors , in vitro , enzyme
Proliferation and differentiation of capillary endothelial cells (i.e., angiogenesis) are essential for breast tumor growth and metastasis. We have recently shown that dolichol‐linked oligosaccharide (i.e., LLO) biosynthesis and turnover are required for angiogenesis. Its inhibition by a glycotherapeutic, tunicamycin resulted in cell cycle arrest in G1 and induction of apoptosis mediated by unfolded protein response ( upr ) signaling. The objective of our study was to evaluate that tunicamycin reduces the survival potential of capillary endothelial cells. We have used vascular endothelial growth factor (VEGF) and insulin‐like growth factor‐1 (IGF‐1) to answer this question. VEGF 165 (10ng/ml) stimulated cellular proliferation but it could not protect the cells from tunicamycin. A similar result was also obtained when the cells were treated with IGF‐1 (10ng/ml). There was however upregulation of p85PI3K(Tyr), Akt(S473) and p53(S15) phosphorylation in tunicamycin treated cells following IGF‐1 treatment for 10 min. The phosphorylation of NFκB (p65 S536) on the other hand remained silent under the experimental condition. These results together with the activation of caspase‐9, p21 and down‐regulation of GSK3‐β following tunicamycin treatment in the absence of IGF‐1 suggest shifting of the survival potential of VEGF 165 /IGF‐1 to apoptosis. Supported in part by grants U54‐CA096297 and Susan G. Komen for Cure BCTR0600582 (DKB), and G12‐RR03035 (KB).