Topoisomerase Inhibitor
Mitoxantrone is a type II topoisomerase inhibitor with IC50 of 2.0 μM, 0.42 mM for HepG2 and MCF-7/wt cells, respectively.
Mitoxantrone 2HCl (100 mg)
£120.00
SKU: BSV-S2485-100
Target: Topoisomerase II
Chemical name: 1,4-dihydroxy-5,8-bis(2-(2-hydroxyethylamino)ethylamino)anthracene-9,10-dione dihydrochloride
Formula: C22H29ClN4O6.2HCl
Molecular weight: 517.4
Purity: 99.36 %
Solubility: 89 mg/mL (DMSO), 89 mg/mL (water)
Size: 100 mg
Storage: 3 years -20°C powder, 2 years -80°C in solvent
In vitro:
Mitoxantrone induces DNA fragmentation and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), a marker of the activation of caspases, in all the patients studied, demonstrating that the cytotoxic effect of mitoxantrone is due to induction of apoptosis. [1] Mitoxantrone activates NFkappaB and stimulates IkappaBalpha degradation in the promyelocytic leukemia cell line HL60 but not in the variant cells, HL60/MX2 cells, which lack the beta isoform of topoisomerase II and express a truncated alpha isoform that results in an altered subcellular distribution. [2] Mitoxantrone inhibits proliferation of activated PBMCs, B lymphocytes, or antigen-specific T-cell lines (TCLs) stimulated on antigen-presenting cells (APCs) in a dose-dependent manner. Mitoxantrone induces apoptosis of PBMCs, monocytes and DCs at low concentrations, whereas higher doses causes cell lysis. [3]
In vivo:
Mitoxantrone transiently decreases the growth rate of HID xenografts in mice but does not affect that of PAC120 xenografts. [4] Mitoxantrone results in the severity of the cardiac lesions and the nephropathy and the intestinal toxicity in spontaneously hypertensive rats. Mitoxantrone and iron(III) form a strong 2:1 complex, in which mitoxantrone may be acting as a tridentate ligand. [5]
References:
[1] Seitz M. Curr Opin Rheumatol, 1999, 11(3), 226-232.
[2] Hirata S, et al. Arthritis Rheum, 1989 , 32(9), 1065-1073.
[3] Segal R, et al. Semin Arthritis Rheum, 1990, 20(3), 190-200.
[4] Hirata S, et al. Arthritis Rheum, 1989, 32(9), 1065-1073.
[5] Genestier L, et al. J Clin Invest, 1998, 102(2), 322-328.
[6] Cronstein BN, et al. J Clin Invest, 1993, 92(6):2675-2682.