Parker, Belinda S. published the artcileMitoxantrone mediates demethylation and reexpression of cyclin D2, estrogen receptor and 14.3.3σ in breast cancer cells, Quality Control of 122110-53-6, the publication is Cancer Biology & Therapy (2003), 2(3), 259-263, database is CAplus and MEDLINE.
In addition to its action as a topoisomerase II poison, mitoxantrone is activated by formaldehyde to bind DNA, forming DNA-adducts specifically at 5’CpG and CpA sequences, with an enhancement of adducts at methylated CpG sites. The butyric acid prodrug, AN-9 (pivaloyloxymethyl butyrate), releases formaldehyde upon cellular hydrolysis and our previous studies have shown that mitoxantrone acts synergistically with AN-9 in cytotoxicity assays. In this paper, we investigated the impact of methylation levels in the cell on mitoxantrone-induced cytotoxicity using the colon cancer cell line HCT116 and its derived DNA methyltransferase (DNMT) 1 and DNMT 3a knockout (DKO8) cell line. We found that decreased methylation levels in the DNMT-null cells led to at least a 2-fold reduction in mitoxantrone-induced cytotoxicity. Next, we studied the impact of mitoxantrone alone, and in combination with AN-9, on hypermethylated genes and their mRNA expression in breast cancer cells. Using methylation-specific PCR and RT-PCR, we found that mitoxantrone treatment of breast cancer cell lines resulted in demethylation of the 14.3.3σ, cyclin D2 and ERα genes, followed by re-expression of their mRNA. The effect of mitoxantrone on re-expression of key genes involved in cell cycle regulation, and ensuing death of the cells may be an addnl., previously undiscovered mechanism of action of mitoxantrone.
Cancer Biology & Therapy published new progress about 122110-53-6. 122110-53-6 belongs to esters-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Ester,Inhibitor, name is (Pivaloyloxy)methyl butyrate, and the molecular formula is C10H18O4, Quality Control of 122110-53-6.
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