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Fig. 9.5
Inhibition of angiogenesis in the CAM assay by MAb3D5AB1, a monoclonal anti-
body against the
-subunit of ATP synthase. Chicken chorioallantoic membranes (CAM) were
treated with 100 ng bFGF with or without ATP synthase inhibitors dissolved on a Thermanox
disc. Vascular growth, branching, and density were assessed after three days, and each CAM was
assigned a composite score between one and six by an investigator blinded to the treatment groups.
A score of one indicates no increased vascularization. Representative images of membranes treated
with 100 ng bFGF alone (
a
), bFGF + 8
α
g angiostatin (
c
)
are shown.
d
) Composite CAM scores for membranes treated with PBS (
1
), bFGF (
2
), bFGF +
MAb3D5AB1 (
3
), and bFGF + angiostatin (
4
) indicate inhibition of bFGF-induced angiogenesis
by MAb3D5AB1 and angiostatin. (Figure 6 reprinted with permission from Chi et al. [15])
μ
g MAb3D5AB1 (
b
), or bFGF + 30
μ
The antibiotic sangivamycin (4-amino-5-carboxamide-7-(D-ribofuranosyl)
pyrrolo[2,3-
d
]pyrimidine), which has previously been shown to specifically inhibit
endothelial cell proliferation, also inhibits angiogenesis, purportedly through
binding to cell surface ATP synthase [22, 29]. Sangivamycin inhibits cell surface
ATP production and blood vessel formation in the CAM model. In addition, the
drug decreases angiogenesis stimulated by Lewis lung carcinoma cells in the
murine dorsal air sac (DAS) assay. Komi et al. hypothesize that sangivamycin,
which is structurally similar to adenosine, acts as a competitive antagonist of F
1
ATP synthase. This group does not address whether sangivamycin also enters
mitochondria and inhibits mitochondrial ATP synthase, given that the antibiotic can
cross the plasma membrane. Sangivamycin also has known inhibitory effects on
protein kinase C, rhodopsin kinase, protein kinase A,
β
-adrenergic receptor kinase,
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