Mitoxantrone (mitozantrone) |
| Catalog No.GC32714 |
Mitoxantrone (mitozantrone) is a potent topoisomerase II inhibitor.
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Cas No.: 65271-80-9
Sample solution is provided at 25 µL, 10mM.
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Mitoxantrone is an antitumor anthrandione derivative. As a potent inhibitor of topoisomerase II, Mitoxantrone can inhibit DNA replication and induce single and double strand breaks through hydrogen bond insertion into DNA. Mitoxantrone is an inhibitor of mitochondrial calcium monotransporter (MCU), which can inhibit calcium entering into mitochondria and prevent mitochondrial calcium overload [1-3]. Mitoxantrone also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 µM.
Mitoxantrone(0.5µg/ml; 48h) induced DNA fragmentation and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), the cytotoxic effect of mitoxantrone was due to induction of apoptosis[4]. Mitoxantrone (50 nM; 24 h) reduced the triglyceride (TG) levels and total cholesterol levels in LMH cells(a steatosis cell model). Mitoxantrone improves hepatic steatosis in broilers as well as reduces circulating lipid levels and fat accumulation in broilers[5].
After mitoxantrone treatment(0-3.2 mg/kg/day; i.p; on days 1, 5, and 9 following tumor inoculation), the increase life span (ILS) of tumor-bearing mice increased by more than 100%[6]. Mitoxantrone persistently suppresses B cells in vivo and led to an enrichment of neutrophils and immunomodulatory CD8(low) T cells[7].
References:
[1]. Nathanson L. Mitoxantrone. Cancer Treat Rev. 1984 Dec;11(4):289-93. doi: 10.1016/0305-7372(84)90025-2. PMID: 6534511.
[2]. Durr FE, Wallace RE, et,al. Molecular and biochemical pharmacology of mitoxantrone. Cancer Treat Rev. 1983 Dec;10 Suppl B:3-11. doi: 10.1016/0305-7372(83)90016-6. PMID: 6362876.
[3]. Arduino DM, Wettmarshausen J, et,al. Systematic Identification of MCU Modulators by Orthogonal Interspecies Chemical Screening. Mol Cell. 2017 Aug 17;67(4):711-723.e7. doi: 10.1016/j.molcel.2017.07.019. PMID: 28820965; PMCID: PMC5825229.
[4]. Bellosillo B, Colomer D, et,al. Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6. doi: 10.1046/j.1365-2141.1998.00520.x. PMID: 9450803.
[5]. Vibet S, MahÉo K, et,al. Differential subcellular distribution of mitoxantrone in relation to chemosensitization in two human breast cancer cell lines. Drug Metab Dispos. 2007 May;35(5):822-8. doi: 10.1124/dmd.106.013474. Epub 2007 Feb 12. PMID: 17296624.
[6]. Fujimoto S, Ogawa M. Antitumor activity of mitoxantrone against murine experimental tumors: comparative analysis against various antitumor antibiotics. Cancer Chemother Pharmacol. 1982;8(2):157-62. doi: 10.1007/BF00255476. PMID: 7105379.
[7]. Chanvillard C, Millward JM, et,al. Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis. PLoS One. 2012;7(6):e39625. doi: 10.1371/journal.pone.0039625. Epub 2012 Jun 29. PMID: 22768101; PMCID: PMC3387260.
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