Cell lines

DPSCs and HDFs

Preparation method

The solubility of this compound in DMSO is >18.2 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

5, 20, 50, 100 and 150 nM

Applications

Mitoxantrone HCl almost completely inhibited DPSCs and HDFs proliferation without causing significant decrease in cell viability after 6 days. Mitoxantrone HCl, at higher doses, i.e. 100 nM and 150 nM, significantly decreased DPSCs and HDFs viability after 3 days. In addition, Mitoxantrone HCl at doses over 50 nM significantly increased the activity of caspases 3/7 and the level of puma, inducing DPSCs and HDFs apoptosis.

Animal models

Mice bearing PAC120 and HID xenografts

Dosage form

1 mg/kg; i.p.; once per 3 weeks

Applications

In mice bearing PAC120 xenografts, Mitoxantrone HCl was well tolerated, although it caused a weight loss of 10% or less. However, it did not inhibit tumor growth. In mice bearing HID xenografts, Mitoxantrone HCl transiently inhibited tumor growth with the optimal effect 3 weeks after the start of treatment. After 30 days, Mitoxantrone HCl no longer exhibited any inhibitory effect on tumor growth.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Mitoxantrone is a Topoisomerase II inhibitor, an anti-neoplastic drug for leukemia and other types of cancer, and a proven drug for multiple sclerosis.

Topoisomerase regulates and changes the topologic conditions of DNA during transcription. It plays a role in condensation of chromosome, separation of chromatid and the relief of torsional stress etc.

Mitoxantrone suppressed the leukemia via inhibiting DNA synthesis and cell cycle progression. It had effect on different immune cells (e.g. T cell, B cell and macrophage etc.) [1] It interfered with TOPO-II-mediated DNA cleavage and led to multiple DSB (DNA strand breaks), chromatin structure changes etc. [2] In PDA (pancreatic ductal adenocarcinoma) cell line, mitoxantrone affected cell survival with IC50< 10 nM and targeted USP11 (human ubiquitin-specific peptidase 11). [3] In human dental pulp stem cells and human dermal fibroblasts, mitoxantrone induced apoptosis or premature senescence in a dose –dependent manner. [4]

In clinical trial, mitoxantrone exhibited a significant but partial efficacy in decreasing the chance of multiple sclerosis progression and relapses frequency in patient with worsening RRMS, PRMS and SPMS in a 2 years follow-up study. [5]

References:
[1] Fox EJ.  Mechanism of action of mitoxantrone. Neurology. 2004 Dec 28;63(12 Suppl 6):S15-8.
[2] Awasthi P, Dogra S, Barthwal R.  Multispectroscopic methods reveal different modes of interaction of anticancer drug mitoxantrone with Poly(dG-dC).Poly(dG-dC) and Poly(dA-dT).Poly(dA-dT). J Photochem Photobiol B. 2013 Oct 5;127:78-87. 
[3] Burkhart RA, Peng Y, Norris ZA et al.  Mitoxantrone targets human ubiquitin-specific peptidase 11 (USP11) and is a potent inhibitor of pancreatic cancer cell survival.  Mol Cancer Res. 2013 Aug;11(8):901-11.
[4] Seifrtova M, Havelek R, Soukup T, Filipova A, Mokry J, Rezacova M.  Mitoxantrone ability to induce premature senescence in human dental pulp stem cells and human dermal fibroblasts.  J Physiol Pharmacol. 2013 Apr;64(2):255-66.
[5] Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G.  Mitoxantrone for multiple sclerosis.  Cochrane Database Syst Rev. 2013 May 31;5:CD002127.