Curcumin Down-Regulates DNA Methyltransferase 1 and Plays an Anti-Leukemic Role in Acut... - 0 views
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In a variety of solid tumors and blood cancers, aberrant hypermethylation of CpG-rich regions (>55% CG content, 0.5-4 kb in length, the so-called “CpG islands”) in the promoters of tumor suppressor genes (TSGs) results in their transcriptional silencing
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These agents have been reported to suppress tumor growth by reversing aberrantly hypermethylation in the promoters of inactivated TSGs (e.g. p15INK4B), allowing re-expression of TSGs, thereby restoring normal cell cycle regulation, proliferation, apoptosis, and differentiation
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groups have reported that curcumin acts as a scavenger of free radicals [13], an inhibitor of NF-κB nuclear translocation [14], and a modulator of histone deacetylase (HDAC) and histone acetyltransferase (HAT)
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In this study, we found that curcumin down-regulated DNMT1 expression in AML cells. This occurred, at least in part, through down-modulation of two positive regulators of DNMT1: Sp1 and the NF-κB component, p65. We also found that curcumin-mediated down-regulation of DNMT1 was associated with reactivation of TSGs and tumor suppression, both in vivo and in vitro.
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Surprisingly, although curcumin significantly inhibited tumor growth in these mice, we were unable to find any obvious toxicity associated with curcumin treatment
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Consistent with our observations regarding curcumin’s ability to inhibit tumor growth in vivo (Figure 4) and down-regulate DNMT1 expression in vitro and ex vivo (Figure 1), we found that decreased levels of DNMT1 protein and mRNA were expressed by tumor cells isolated from curcumin-treated mice
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we identified curcumin as a substance which acts as an inhibitor of DNA methyltransferase enzymatic activity and induces significant global DNA hypomethylation in AML cells
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In this study, we first demonstrated that curcumin decreases DNMT1 mRNA and protein expression levels, most likely through inhibiting expression of positive regulators of DNMT1, such as Sp1 and the p65 component of NF-κB component, and/or altering their ability to bind to the promoter region of DNMT1