Topotecan HCl is a topoisomerase I inhibitor that acts as a Topo I poison. Topotecan HCl specifically targets the topoisomerase I–DNA cleavage complex, acting after DNA cleavage and inhibiting the re-ligation step. Topotecan HCl can cross the blood–brain barrier and exhibits cytotoxicity against a variety of tumor cell types, showing significant activity in the treatment of brain tumors[1].
In vitro, Topotecan HCl (0.02-40μM; 12-48h) dose- and time-dependently inhibited the proliferation of U251, U87, GSCs-U251, and GSCs-U87 cells, with IC₅₀ values at 24h of 2.73±0.25, 2.95±0.23, 5.46±0.41, and 5.95±0.24μM, respectively[1]. Topotecan HCl (3μM; 24h) significantly upregulated p21 protein levels and induced cell cycle arrest at the G0/G1 and S phases in U251, U87, GSCs-U251, and GSCs-U87 cells[1]. Topotecan HCl (0.1-1000ng/mL; 72h) caused a dose-dependent reduction in the viability of HUVECs, with an IC₅₀ of 4.87ng/mL[2]. Among neuroblastoma cell lines, the IC50 values of Topotecan HCl on SH-SY5Y, BE(2)-c and SK-N-BE(2) were 5.3ng/mL, 45.6ng/mL and 65.0ng/mL, respectively. Among sarcoma cell lines, the IC50 values of Topotecan HCl on RH30, RD, and KHOS cell lines were 7.4ng/mL, 7.5ng/mL, and 4.9ng/mL, respectively[2].
In vivo, Topotecan HCl (1mg/kg/d; p.o.; 56d) significantly improved the survival of nonobese diabetic/severe combined immune deficient (NOD/SCID) mice bearing SK-N-BE (2)[2]. In IGROV-1 tumour-bearing mice, Topotecan HCl (10mg/kg) given intraperitoneally every 4 days for four occasions markedly increased survival time over control mice[3].
References:
[1] Zhang FL, Wang P, Liu YH, et al. Topoisomerase I inhibitors, shikonin and Topotecan HCl, inhibit growth and induce apoptosis of glioma cells and glioma stem cells. PLoS One. 2013;8(11):e81815.
[2] Kumar S, Mokhtari RB, Sheikh R, et al. Metronomic oral Topotecan HCl with pazopanib is an active antiangiogenic regimen in mouse models of aggressive pediatric solid tumor. Clin Cancer Res. 2011;17(17):5656-5667.
[3] Pratesi G, Tortoreto M, Corti C, Giardini R, Zunino F. Successful local regional therapy with Topotecan HCl of intraperitoneally growing human ovarian carcinoma xenografts. Br J Cancer. 1995;71(3):525-528.