Tetracationic porphyrins inhibit angiogenesis induced by human tumor cells in vivo.
BACKGROUND
Cationic porphyrin TMPyP4, but not its isomer TMPyP2, inhibits telomerase in tumor cells in vitro and induces chromosome destabilization in vivo.


METHODS
To examine the effects of these porphyrins on tumor-induced angiogenesis, 25-200 micrograms TMPyP4 or TMPyP2 were injected daily for 3 days in mice with intradermally implanted primary human tumor cells. Alternatively, tumor cells were exposed for 90 minutes to 2.5-20 microM porphyrins prior to implantation in mice.


RESULTS
Either subcutaneous injections (> or = 50 micrograms/mouse) or preincubation with > or = 5 microM porphyrins significantly inhibited angiogenesis.


CONCLUSIONS
Antiangiogenic activity is apparently unrelated to the ability of the porphyrins to inhibit telomerase.
Izbicka
E
E
Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX 78245, USA. eizbicka@saci.org
Sommer
E
E
Skopinska-Rozewska
E
E
Davidson
K
K
Wu
R S
RS
Orlowski
T
T
Pastewka
K
K
D018262:Adenocarcinoma, Clear Cell / Q000098:blood supply / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000098:blood supply / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000098:blood supply / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000473:pathology; D008175:Lung Neoplasms / Q000098:blood supply / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic; D010894:Piroxicam / Q000494:pharmacology; D011166:Porphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011166:Porphyrins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D010894:Piroxicam; C021096:tetra(4-N-methylpyridyl)porphine; C057456:tetra(2-N-methylpyridyl)porphine; D001241:Aspirin