Mitoxantrone: A New Anticancer Drug with Significant Clinical Activity

Abstract

Clinical studies using mitoxantrone, an anthraquinone, were begun in the United States in 1979. Subsequent phase II and III trials have shown that mitoxantrone has significant clinical activity in patients with breast cancer, acute leukemia, and lymphoma. The drug has antiviral, antibacterial, antiprotozoal, immunomodulating, and antineoplastic properties and is mutagenic in some animal systems. Its mechanism of action seems to involve both DNA intercalation and nonintercalative electrostatic interactions. The dose-limiting toxicity is myelosuppression when the drug is given on a single-dose, every-3-week schedule and mucositis when it is given daily for 5 days. Other toxicities include gastrointestinal and cardiac effects, the gastrointestinal toxicity being less severe and less frequent than that with the anthracycline anticancer drugs. Because of its low incidence of serious toxicities and effectiveness in treating certain solid tumors and leukemias, mitoxantrone is a promising new agent in the treatment of cancer.

Spectral analysis of the DNA targeting bisalkylaminoanthraquinone DRAQ5 in intact living cells

“…The concept of targeting DNA damaging agents to specific DNA sequences has led to a search for enhanced DNAaffinic properties of DNA intercalators and minor groove binders (1,(31)(32)(33). Reporter molecules with distinct and informative fluorescence profiles that can rapidly form equilibria within nuclear compartments can aid the building of pharmacokinetic models to support drug development and deployment.…”

Gold nanostars for efficient in vitro and in vivo real-time SERS detection and drug delivery via plasmonic-tunable Raman/FTIR imaging

“…Furthermore, MTX has antiviral, antibacterial, antiprotozoal, immunomodulating, and antineoplastic properties and is mutagenic in some animal systems. 32 Moreover, MTX has a red fluorescence emission as well as a strong Raman scattering signal with gold nanoparticles. The Raman signals of MTX molecules were evaluated by the plasmonic field of GNPs, depending on the distance between the drug molecules and the nanoparticle's surface.…”

Natural resistance of acute myeloid leukemia cell lines to mitoxantrone is associated with lack of apoptosis

“…Mitoxantrone binds extensively to nucleic acids by intercalation 24 and this binding may explain the ability of mitoxantrone to cause condensation and compaction of chromatin, 25 dissociation of DNA-bound proteins 26 as well as inhibition of DNA, RNA, and protein synthesis. 10 Although it has been proposed that mitoxantrone-induced DNA lesions may also arise age arising from this interaction may explain the observed long-term inhibition of DNA synthesis, cell arrest in the G 2 phase of the cell cycle, and subsequent cell death. 30 Resistance to mitoxantrone has been extensively studied over the last few years.…”

“…[10][11][12] The cytotoxic action Acute myeloid leukemia (AML) is a neoplastic disorder of mitoxantrone is believed to be associated with its ability to characterized by the clonal expansion of leukemic myeloid stabilize a covalent DNA-topoisomerase II reaction product, cells. In spite of apparent uniformity, AML cells consist of a the so-called cleavable complex (for review see Ref.…”

“…In spite of apparent uniformity, AML cells consist of a the so-called cleavable complex (for review see Ref. 10). More heterogeneous cellular population.…”