Inhibition of angiogenesis by the antineoplastic agents mitoxantrone and bisantrene.
The effects of mitoxantrone and bisantrene on angiogenic responses induced by tumor cell-conditioned media in the avascular cornea of rat eye have been evaluated. Both mitoxantrone and bisantrene effectively inhibited, in a concentration-dependent manner, angiogenesis induced by conditioned media obtained from either a hamster buccal pouch carcinoma cell line or P388D1 murine macrophage-like cells. Whereas vessel ingrowth in corneas containing tumor cell-conditioned media was detected as early as day 2 or 3 and was maximal by day 7, inclusion of mitoxantrone or bisantrene in the conditioned media at a 1:1 ratio (160 microM mitoxantrone or 32 microM bisantrene) resulted in complete inhibition of angiogenesis throughout the 14-day evaluation period. When concentrations of 64 and 32 microM mitoxantrone or 13 and 6.4 microM bisantrene were employed there was a marked delay in the appearance of capillary blood vessels (day 5 to 7) and a reduction in the intensity of angiogenic responses. No untoward toxicity to the tissue was observed at the concentrations of mitoxantrone or bisantrene employed.
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003315:Cornea / Q000098:blood supply; D003470:Culture Media; D008942:Mitoxantrone / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D051381:Rats
D000873:Anthracenes; D000970:Antineoplastic Agents; D003470:Culture Media; C031404:bisantrene; D008942:Mitoxantrone