Anti-tumor activities of chondroitinase AC and chondroitinase B: inhibition of angiogenesis, proliferation and invasion

• Published in: European journal of pharmacology Vol. 416; no. 3; pp. 213 - 221
• Main Authors: Denholm, Elizabeth M., Lin, Yong-Qing, Silver, Paul J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30-03-2001; Elsevier
• Subjects: Animal tumors. Experimental tumors; Animals; Antineoplastic agents; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cattle; Cell Division - drug effects; Cell Movement - drug effects; Cells, Cultured; Chemotherapy; Chondroitin sulfate; Chondroitin Sulfates - physiology; Chondroitinase; Chondroitinases and Chondroitin Lyases - pharmacology; Dermatan; Dermatan Sulfate - physiology; Dose-Response Relationship, Drug; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Experimental cardiovascular tumors; Gelatinases - metabolism; Humans; Medical sciences; Melanoma - pathology; Metastasis; Neoplasm Metastasis; Neovascularization, Pathologic; Neovascularization, Physiologic - drug effects; Pharmacology. Drug treatments; Proliferation; Tumor Cells, Cultured; Tumors; Chondroitin sulfate; Metastasis; Proliferation; Dermatan; Chondroitinase; Apoptosis; Antineoplastic agent; Cell proliferation; Proteoglycan; Polysaccharide-lyases; Endothelial cell; Enzyme; Melanoma; Lyases; In vitro; Biological activity; Angiogenesis; Mechanism of action; Carbon-oxygen lyases; Tumor cell; Chondroitin AC lyase
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)00884-6

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.