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Superior antiproliferative activity of histone deacetylase inhibitor apicidin and proteasome inhibitors against human colorectal cancer cells
Author(s) -
Abaza Mohamed Salah,
Bahman AbdulMajeed,
AlAttiyah Rajaa
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.964.4
Subject(s) - histone deacetylase , cancer research , cancer cell , histone deacetylase inhibitor , cancer , proteasome inhibitor , proteasome , colorectal cancer , apoptosis , downregulation and upregulation , cell cycle , chemistry , pharmacology , biology , medicine , histone , biochemistry , gene
The aim of this study was to determine what effect proteasome inhibitors (PSIs) would exert on the response of human colorectal cancer cells to histone deacetylase inhibitor(HDACI) apicidin and also to examine the molecular mechanisms of the combined treatment with apicidin and PSIs as well as its potential to sensitize cancer cells to chemotherapeutic drugs. Growth inhibition of cancer cells by apicidin was potentiated to various degrees in the presence of PSIs in a dose dependent manner. The combinations of apicidin and various PSIs growth arrested colorectal cancer cells in G2‐phase, Go‐G1/S‐phases and S/G2‐M phases in a combination dependent manner. Also, these combinations induced more potent apoptosis compared to single treatment with apicidin and PSIs. Upregulation of p16, p19, p21, p57, caspase‐3, caspase‐3, Bim, Apaf1, Bad and Bak mRNAs and downregulation of Cdk1, Cdk4, Cdk6, Bcl2, cIAP1 and cIAP2 mRNAs were observed. The combinations of apicidin and various PSIs chemosensitized cancer cells to chemotherapeutic drugs. These findings indicated that coadministration of apicidin and PSIs are associated with enhanced antiproliferative activity, apoptosis and chemosensitization of human colorectal cancer cells to conventional chemotherapeutic drugs through selective induction and suppression of genes that play an important role in the cell cycle and apoptosis.