Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0029463 (
osteosarcoma
)
16,637
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mithramycin
(
MTR
) is a clinically approved DNA-binding antitumor antibiotic currently in Phase 2 clinical trials at National Institutes of Health for treatment of
osteosarcoma
. In view of the resurgence in the studies of this generic antibiotic as a human medicine, we have examined the binding properties of
MTR
with the integral component of chromatin - histone proteins - as a part of our broad objective to classify DNA-binding molecules in terms of their ability to bind chromosomal DNA alone (single binding mode) or both histones and chromosomal DNA (dual binding mode). The present report shows that besides DNA,
MTR
also binds to core histones present in chromatin and thus possesses the property of dual binding in the chromatin context. In contrast to the
MTR
-DNA interaction, association of
MTR
with histones does not require obligatory presence of bivalent metal ion like Mg(2+). As a consequence of its ability to interact with core histones,
MTR
inhibits histone H3 acetylation at lysine 18, an important signature of active chromatin, in vitro and ex vivo. Reanalysis of microarray data of Ewing sarcoma cell lines shows that upon
MTR
treatment there is a significant down regulation of genes, possibly implicating a repression of H3K18Ac-enriched genes apart from DNA-binding transcription factors. Association of
MTR
with core histones and its ability to alter post-translational modification of histone H3 clearly indicates an additional mode of action of this anticancer drug that could be implicated in novel therapeutic strategies.
...
PMID:Anticancer drug mithramycin interacts with core histones: An additional mode of action of the DNA groove binder. 2547 95
