Suppression of tumor growth by a new glycosaminoglycan isolated from the African giant snail Achatina fulica.
Acharan sulfate is a new type of glycosaminoglycan from the giant African snail, Achatina fulica. Acharan sulfate, which has a primary repeating disaccharide structure of alpha-D-N-acetylglucosaminyl-2-O-sulfo-alpha-L-iduronic acid, was studied as a potential antitumor agent in both in vivo and in vitro assays. The antiangiogenic activity of acharan sulfate was evaluated in the chorioallantoic membrane assay and by measuring its effect on the proliferation of calf pulmonary artery endothelial cells. In vivo, a matrigel plug assay showed that acharan sulfate suppressed basic fibroblast growth factor (bFGF)-stimulated angiogenesis and lowered the hemoglobin (Hb) content inside the plug. Acharan sulfate was administered s.c. at two doses for 15 days to C57BL/6 mice implanted with murine Lewis lung carcinoma in the back. It was also administered i.p. to ICR mice bearing sarcoma 180 at a dose of 30 mg/kg. Subcutaneous injection of acharan sulfate at doses of 10 and 30 mg/kg decreased tumor weight and tumor volume by 40% without toxicity or resistance. Intraperitoneal injection of acharan sulfate also decreased tumor weight and volume by 40% in sarcoma 180-bearing mice. These results suggest that the antitumor activity of acharan sulfate may be related to the inhibition of angiogenesis.
Lee
Yeon Sil
YS
Natural Products Research Institute, College of Pharmacy, Seoul National University, 28 Yeonkun-Dong, Jongno-Ku, Seoul, 110-460, South Korea.
Yang
Hyun Ok
HO
Shin
Kuk Hyun
KH
Choi
Hyung Seok
HS
Jung
Sang Hoon
SH
Kim
Yong Man
YM
Oh
Deok Kun
DK
Linhardt
Robert J
RJ
Kim
Yeong Shik
YS
D000482:Allantois / Q000098:blood supply / Q000187:drug effects; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006025:Glycosaminoglycans / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D012513:Sarcoma, Experimental / Q000473:pathology / Q000517:prevention & control; D012908:Snails / Q000737:chemistry*; D013047:Specific Pathogen-Free Organisms; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D006025:Glycosaminoglycans; C106771:acharan sulfate