Premium
Anti‐angiogenic Potential of Tunicamycin is NOT Reversible by Vascular Endothelial Growth Factor VEGF 165
Author(s) -
Banerjee A,
Baksi K.,
Burgos M.,
Banerjee D. K.
Publication year - 2008
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.22.1_supplement.809.2
Subject(s) - tunicamycin , angiogenesis , vascular endothelial growth factor , cancer research , vascular endothelial growth factor a , medicine , chemistry , pharmacology , apoptosis , immunology , endocrinology , biology , vegf receptors , unfolded protein response , biochemistry
Angiogenesis is essential for tumor progression. Current approaches inhibiting angiogeneis and eliminating breast tumor growth had limited success. Our laboratory has been focusing on glycotherapeutics and studying the dynamic relationship between the lipid‐linked oligosaccharide biosynthesis and angiogenesis. We have previously observed that tunicamycin, an N‐acetylglucosaminyl 1‐phopshate transferase inhibitor arrested capillary endothelial cells in G1, developed unfolded protein response and induced apoptosis. Reduced expression of Bcl‐2, cyclin D1 and PCNA has confirmed it. To evaluate if the anti‐angiogenic potential of tunicamycin could sustain the tumor–derived cytokine(s), we have used VEGF. Cells cultured with VEGF 165 (10–100 ng/ml) supported proliferation but failed to overcome the tunicamycin inhibition. Total VEGF receptor‐1 (Flt‐1) expression has remained unchanged in G1 but maximally activated after 3 hours of VEGF treatment. Total and the activated VEGF receptor were however reduced after 3 and 12 hours of tunicamycin treatment. Thus, we conclude that VEGF is unable to neutralize the anti‐angiogenic potential of tunicamycin. Supported by NIH U54‐CA096297 and Susan G. Komen Breast Cancer Foundation BCTR5820 (DKB), and NIH/NCRR/RCMI grant G12‐RR03035 (KB).