Histone deacetylase inhibitors (HDACIs) represent a new class of targeted anti-
cancer agents and different other diseases, like muscular disorders. A number of studies have shown that extracellular signal-activated
kinases can target
chromatin-modifying complexes directly and regulate their function. The molecular connection between the
dystrophin-associated protein complex (
DAPC) and
chromatin has been described, by showing that NO signaling regulates
histone deacetylase (HDAC) activity and influences gene expression in different cell types. In present study, we investigated HDACs changes in HeLa cells undergoing growth inhibition and apoptosis, caused by HDACI
BML-210 and
retinoic acid (ATRA). Cell cycle analysis indicated that HeLa cell treatment with 20 and 30 μM concentration of
BML-210 increased the proportion of cells in G0/G1 phase, and caused accumulation in subG1, indicating that the cells are undergoing apoptosis. We determined down-regulation of HDAC 1-5 and 7
after treatment with
BML-210. Also, we demonstrated expression of different
isoforms of
alpha-dystrobrevin (α-DB) and other components of
DAPC such as
syntrophin,
dystrophin,
beta-dystrobrevin (β-DB) and NOS in HeLa cells
after treatments. We determined changes in
protein expression level of
dystrophin, NOS1, α- and β-DB and in subcellular localization of α-DB
after treatments with
BML-210 and ATRA. In conclusion, these results suggest that HDACI
BML-210 can inhibit cell growth and induce apoptosis in
cervical cancer cells, what correlates with down-regulation of HDAC class I and II and changes in the
DAPC expression levels. This can be important for identifying target
proteins in
DAPC signaling to HDACs, as a target of pharmacological intervention for treatment of
muscular dystrophies and other diseases.