Angiogenesis inhibitor TNP-470: Cytotoxic effects on human neoplastic celllines

Angiostatic substance TNP-470 displayed moderate cytotoxicity towards human leukemia HL-60, HL-60/ADR, HL-60/VCR and myeloma ARH77 cell lines with IC5 0 in the range 5-10 mu M of concentrations and slightly higher IC50 for mye loma cell line U266. IC50 for ovarian CH-1, A2780 and A2780/ADR cell lines was in the range 10-15 mu M with the exception of platinum-resistant SKOV3 cell line (more than 40 mu M). The IC50 values for MDA-MB-231 and MCF-7 bre ast carcinoma cell lines were 15 and 25 mu M, respectively. In human hemopo ietic neoplastic cell lines examined, TNP-470 induced the appearance of sub population with sub-G0 DNA content, suggesting the apoptosis-inducing poten tial of TNP-470 in these cells. No TNP-470-induced drug uptake modulation i n drug-resistant leukemia cell line HL-60/VCR was observed. TNP-470 induced accumulation of cells in G0/G1 phase of cell cycle. There was no TNP-470-i nduced inhibition of MMP collagenase activity or MMP (MMP2 and MMP9) produc tion in the human fibrosarcoma cells HT1080 in vitro.