Efficacy of decitabine-loaded nanogels in overcoming cancer drug resistance is mediated via sustained DNA methyltransferase 1 (DNMT1) depletion
S Vijayaraghavalu, V Labhasetwar - Cancer letters, 2013 - Elsevier
Cancer letters, 2013•Elsevier
DNA methyltransferase 1 (DNMT1) promotes DNA methylation to maintain cancer drug
resistance. The epigenetic drug, decitabine (DAC) is a potent hypomethylating agent, but its
effect is transient because of its instability. We tested the efficacy of DAC-loaded nanogels in
doxorubicin-resistant breast cancer cells, DAC-resistant melanoma cells, and leukemia
cells. DAC in nanogel sustained DNMT1 depletion, prolonged cell arrest in the G2/M cell-
cycle phase, and significantly enhanced antiproliferative effect of DAC. The efficacy of DAC …
resistance. The epigenetic drug, decitabine (DAC) is a potent hypomethylating agent, but its
effect is transient because of its instability. We tested the efficacy of DAC-loaded nanogels in
doxorubicin-resistant breast cancer cells, DAC-resistant melanoma cells, and leukemia
cells. DAC in nanogel sustained DNMT1 depletion, prolonged cell arrest in the G2/M cell-
cycle phase, and significantly enhanced antiproliferative effect of DAC. The efficacy of DAC …
DNA methyltransferase 1 (DNMT1) promotes DNA methylation to maintain cancer drug resistance. The epigenetic drug, decitabine (DAC) is a potent hypomethylating agent, but its effect is transient because of its instability. We tested the efficacy of DAC-loaded nanogels in doxorubicin-resistant breast cancer cells, DAC-resistant melanoma cells, and leukemia cells. DAC in nanogel sustained DNMT1 depletion, prolonged cell arrest in the G2/M cell-cycle phase, and significantly enhanced antiproliferative effect of DAC. The efficacy of DAC-loaded nanogels was more significant in resistant than sensitive cells. Our data suggest that effective delivery of DAC and prolonged DNMT1 depletion are critical to overcoming drug resistance.
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