Antiangiogenic and antimetastatic properties of Neovastat (AE-941), an orally active extract derived from cartilage tissue.
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.
Dupont
Eric
E
Les Laboratoires AEterna Inc, Québec, Canada.
Falardeau
Pierre
P
Mousa
Shaker A
SA
Dimitriadou
Violetta
V
Pepin
Marie-Claude
MC
Wang
Taiqi
T
Alaoui-Jamali
Moulay A
MA
D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001808:Blood Vessels / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D002356:Cartilage / Q000737:chemistry; D002642:Chick Embryo; D002945:Cisplatin / Q000008:administration & dosage; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000633:toxicity; D006801:Humans; D007797:Laminin; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011509:Proteoglycans; D014020:Tissue Extracts / Q000302:isolation & purification / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D014020:Tissue Extracts; C111481:shark cartilage extract; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen; D002945:Cisplatin