Antiangiogenic and antimetastatic properties of Neovastat (AE-941), an orally active extract derived from cartilage tissue.

Abstract

A novel naturally occurring antiangiogenic agent isolated from cartilage, referred to as Neovastat (AE-941), was examined for its efficacy against tumor neovascularization and progression. Exposure to Neovastat results in ex ovo antiangiogenic properties in the chorioallantoid membrane of chicken embryo (71% decrease in the angiogenic index as compared to the basic fibroblast growth factor (bFGF) treated control embryos, P < 0.0001). Oral administration of Neovastat inhibits bFGF-induced angiogenesis in the Matrigel mouse model (87.5% decrease in hemoglobin as compared to the bFGF-treated control implants, P < 0.0001). Neovastat also induces a dose response decrease of lung metastases in the Lewis lung carcinoma model (oral administration; 69.1% of inhibition obtained at the maximal dose of 0.5 ml/day, P < 0.0001). Combined with a sub-optimal dose of cisplatinum (2 mg/kg, i.p.), Neovastat (0.5 ml/day) improved the therapeutic index by increasing the antimetastatic efficacy and by exerting a protective activity against cisplatinum-induced body weight loss and myelosuppression. In summary, our experimental data provide evidence of antiangiogenic and antimetastatic properties of Neovastat, following oral administration.

• Authors: Eric Dupont, Pierre Falardeau, Shaker A Mousa, Violetta Dimitriadou, Marie-Claude Pepin, Taiqi Wang, Moulay A Alaoui-Jamali
• Journal: Clinical & experimental metastasis (Clin Exp Metastasis) Vol. 19 Issue 2 Pg. 145-53 ( 2002) ISSN: 0262-0898 [Print] Netherlands
• PMID: 11964078 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Drug Combinations
• Laminin
• Proteoglycans
• Tissue Extracts
• shark cartilage extract
• Fibroblast Growth Factor 2
• matrigel
• Collagen
• Cisplatin

Topics

• Administration, Oral
• Angiogenesis Inhibitors (isolation & purification, pharmacology)
• Animals
• Antineoplastic Agents (isolation & purification, pharmacology)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Blood Vessels (drug effects)
• Body Weight (drug effects)
• Carcinoma, Lewis Lung (blood supply, drug therapy, pathology)
• Cartilage (chemistry)
• Chick Embryo
• Cisplatin (administration & dosage)
• Collagen
• Dose-Response Relationship, Drug
• Drug Combinations
• Female
• Fibroblast Growth Factor 2 (toxicity)
• Humans
• Laminin
• Mice
• Mice, Inbred BALB C
• Neovascularization, Pathologic (prevention & control)
• Proteoglycans
• Tissue Extracts (isolation & purification, pharmacology)