Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities.
BACKGROUND
A potent angiogenesis inhibitor, U-995, has been purified from the cartilage of the blue shark (Prionace glauca). U-995 is composed of two single peptides with molecular mass of 10 and 14 kDa, respectively.


METHODS
U-995 was designed to study human umbilical vein endothelial cell (HUVEC) migration and proliferation in vitro and angiogenesis induced by TNF alpha in chicken chorioallantoic membrane (CAM). Furthermore, we determined the ability of U-995 to inhibiting tumor cell growth and metastasis.


RESULTS
U-995 (15 and 30 micrograms/ml) markedly inhibited HUVEC migration and, at 15-50 micrograms/ml produced a dose-dependent decline in [3H]-thymidine incorporation. 30 and 50 micrograms/ml of U-995, when added to TNF alpha-induced angiogenesis caused discontinuous and disrupted blood vessels. Moreover, U-995 (30 micrograms/ml) markedly prevented collagenase-induced collagenolysis. In addition, when 200 micrograms U-995 was injected i.p. into mice it suppressed sarcoma-180 cell growth and B16-F10 mouse melanoma cell metastasis in vivo.


CONCLUSIONS
These results suggest that the anti-angiogenic effects of U-995 may be be due to interference with the proliferation and migration of HUVECs as well as inhibition of collagenolysis, thereby leading to inhibition of both angiogenesis and tumor cell growth.
Sheu
J R
JR
Cancer Research Center, Gwo-Chyang GMP Pharmaceutical Co., Ltd., Tainan, Taiwan. acesane@ms4.hinet.net
Fu
C C
CC
Tsai
M L
ML
Chung
W J
WJ
D000482:Allantois; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000627:therapeutic use / Q000633:toxicity*; D002356:Cartilage; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D002823:Chorion; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000517:prevention & control / Q000556:secondary*; D061965:Matrix Metalloproteinase Inhibitors; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D051379:Mice; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010455:Peptides; D011506:Proteins / Q000302:isolation & purification / Q000627:therapeutic use / Q000633:toxicity*; D012510:Sarcoma 180 / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D012754:Sharks; D013936:Thymidine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D010455:Peptides; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; C116988:U 995; D013936:Thymidine