Angiogenesis inhibitor TNP-470: Cytotoxic effects on human neoplastic cell lines

作者：Sedlakova O^*; Sedlak J; Hunakova L; Jakubikova J; Duraj J; Sulikova M; Chovancova J; Chorvath B

来源：Neoplasma, 1999, 46(5): 283-289.

• TNP 470
• angiogenesis inhibitor
• cytotoxic activity in vitro
• apoptosis
• cell cycle alterations
• human leukemia
• myeloma and carcinoma cell lines
• MMP2
• MMP9
• collagen zymography

Angiostatic substance TNP-470 displayed moderate cytotoxicity towards human leukemia HL-60, HL-60/ADR, HL-60/VCR and myeloma ARH77 cell lines with IC50 in the range 5-10 mu M of concentrations and slightly higher IC50 for myeloma 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 breast carcinoma cell lines were 15 and 25 mu M, respectively. In human hemopoietic neoplastic cell lines examined, TNP-470 induced the appearance of subpopulation with sub-G0 DNA content, suggesting the apoptosis-inducing potential of TNP-470 in these cells. No TNP-470-induced drug uptake modulation in 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-induced inhibition of MMP collagenase activity or MMP (MMP2 and MMP9) production in the human fibrosarcoma cells HT1080 in vitro.

• 出版日期1999