Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-153 |
Sentence |
denotes |
Rapid induction of histone hyperacetylation and cellular differentiation in human breast tumor cell lines following degradation of histone deacetylase-1. |
T2 |
154-264 |
Sentence |
denotes |
Quinidine inhibits proliferation and promotes cellular differentiation in human breast tumor epithelial cells. |
T3 |
265-419 |
Sentence |
denotes |
Previously we showed quinidine arrested MCF-7 cells in G(1) phase of the cell cycle and led to a G(1) to G(0) transition followed by apoptotic cell death. |
T4 |
420-597 |
Sentence |
denotes |
The present experiments demonstrated that MCF-7, MCF-7ras, T47D, MDA-MB-231, and MDA-MB-435 cells transiently differentiate before undergoing apoptosis in response to quinidine. |
T5 |
598-688 |
Sentence |
denotes |
The cells accumulated lipid droplets, and the cytokeratin 18 cytoskeleton was reorganized. |
T6 |
689-812 |
Sentence |
denotes |
Hyperacetylated histone H4 appeared within 2 h of the addition of quinidine to the medium, and levels were maximal by 24 h. |
T7 |
813-1111 |
Sentence |
denotes |
Quinidine-treated MCF-7 cells showed elevated p21(WAF1), hypophosphorylation and suppression of retinoblastoma protein, and down-regulation of cyclin D1, similar to the cell cycle response observed with cells induced to differentiate by histone deacetylase inhibitors, trichostatin A, and trapoxin. |
T8 |
1112-1217 |
Sentence |
denotes |
Quinidine did not show evidence for direct inhibition of histone deacetylase enzymatic activity in vitro. |
T9 |
1218-1312 |
Sentence |
denotes |
HDAC1 was undetectable in MCF-7 cells 30 min after addition of quinidine to the growth medium. |
T10 |
1313-1418 |
Sentence |
denotes |
The proteasome inhibitors MG-132 and lactacystin completely protected HDAC1 from the action of quinidine. |
T11 |
1419-1559 |
Sentence |
denotes |
We conclude that quinidine is a breast tumor cell differentiating agent that causes the loss of HDAC1 via a proteasomal sensitive mechanism. |