Anti-tumor activities of chondroitinase AC and chondroitinase B: inhibition of angiogenesis, proliferation and invasion.
In the current study, two specific glycosaminoglycan lyases, chondroitinase AC and chondroitinase B, were utilized to examine the roles of chondroitin sulfates and dermatan sulfate in tumor metastasis and angiogenesis. Melanoma cells (SK-MEL) or endothelial cells were treated with either medium or chondroitinase enzyme. Chondroitinase AC inhibited melanoma invasion and proliferation as well as endothelial proliferation and angiogenesis. Apoptosis of melanoma and endothelial cells, as measured by the activity of caspase-3, was also increased by chondroitinase AC, but not by chondroitinase B. Chondroitinase B inhibited endothelial and melanoma proliferation and invasion, but to a lesser extent than chondroitinase AC. Neither chondroitinase had a detectable effect on gelatinase secretion by melanoma cells. These results indicate that both chondroitin and dermatan sulfates regulate many cellular activities related to metastasis.
Denholm
E M
EM
Department of Cellular Biology, IBEX Pharmaceuticals, Inc., 5485 Pare, H4P 1P7, Montreal, Quebec, Canada. edenholm@ibexpharma.com
Lin
Y Q
YQ
Silver
P J
PJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000502:physiology*; D002810:Chondroitinases and Chondroitin Lyases / Q000494:pharmacology*; D003871:Dermatan Sulfate / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000473:pathology; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates; D018093:Gelatinases; D002810:Chondroitinases and Chondroitin Lyases