Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that breast cancer stem cells (CSCs), which characterized by CD44(+)CD24(-/low), may result in treatment failure in patients with breast cancer. It is possible therefore that that inhibiting such subpopulation might subsequently improve clinical outcome. In the present study, we found that the CD44(+)/CD24(-/low) CSCs, isolated from both human breast cell line MCF-7 and MDA-MB-231, were more resistant to thiotepa, paclitaxel and anthracycline, when compared with the non-breast cancer stem cell subset from the same cell lines, whereas the chemosensitivities were remarkably reversed by higher concentration of thiotepa and paclitaxel except for adriamycin. The percentage of CSCs was significantly decreased with an addition of DNA methyltransferase inhibitor CDA-2 and the expression of Smo, Shh, and Gli-1 of Hedgehog signaling pathway in CSCs was decreased. Of important findings, combination of thiotepa or paclitaxel with CDA-2 could significantly inhibit the proliferation of CSCs regardless of their dosages. These results unveiled that the selection of cytotoxic agents and increasing their dosage might be of great importance in the respect of eliminating CSCs. DNA methyltransferase inhibitor CDA-2 exhibited a synergistic effect with cytotoxic drugs, which might provide a conceptually new therapeutic strategy.
 ...
PMID:DNA methyltransferase inhibitor CDA-2 synergizes with high-dose thiotepa and paclitaxel in killing breast cancer stem cells. 2119 4

CDA-II (cell differentiation agent II), isolated from healthy human urine, is a DNA methyltransferase inhibitor. Previous studies indicated that CDA-II played important roles in the regulation of cell growth and certain differentiation processes. However, it has not been determined whether CDA-II affects skeletal myogenesis. In this study, we investigated effects of CDA-II treatment on skeletal muscle progenitor cell differentiation, migration and proliferation. We found that CDA-II blocked differentiation of murine myoblasts C2C12 in a dose-dependent manner. CDA-II repressed expression of muscle transcription factors, such as Myogenin and Mef2c, and structural proteins, such as myosin heavy chain (Myh3), light chain (Mylpf) and MCK. Moreover, CDA-II inhibited C1C12 cell migration and proliferation. Thus, our data provide the first evidence that CDA-II inhibits growth and differentiation of muscle progenitor cells, suggesting that the use of CDA-II might affect skeletal muscle functions.
 ...
PMID:DNA methyltransferase inhibitor CDA-II inhibits myogenic differentiation. 2262 35