Abstract
A novel hybrid synthetic histone deacetylase inhibitor, SK-7041, was synthesized from hydroaxamic acid of trichostatin A (TSA) and pyridyl ring of MS-275. TSA and SK-7041 both induced apoptosis and G2-M cell cycle arrest in pancreatic cancer cell lines. The expressions of p21 and cyclin D2 were up-regulated and that of cyclin B1 was down-regulated by TSA or SK-7041. The expression levels of Mcl-1 and Bcl-XL but not those of Bcl-2, Bax, and Bak were suppressed by TSA or SK-7041 treatment. SK-7041 or TSA induced apoptosis and G2-M cell cycle arrest by up-regulating p21 and down-regulating cyclin B1, Mcl-1, and Bcl-XL.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / pharmacology*
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Antineoplastic Agents / pharmacology*
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Apoptosis*
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Biphenyl Compounds / pharmacology*
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Cell Division
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Cell Line, Tumor / drug effects
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Cell Proliferation / drug effects*
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Cyclin B / metabolism
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Cyclin B1
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Cyclin D2
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Cyclins / metabolism
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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G2 Phase
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Histone Deacetylase Inhibitors*
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Histone Deacetylases / metabolism
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Histones / metabolism
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Humans
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Hydroxamic Acids / pharmacology
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins / metabolism
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Pancreatic Neoplasms / enzymology*
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Pancreatic Neoplasms / pathology
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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bcl-X Protein / metabolism
Substances
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Amides
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Antineoplastic Agents
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BCL2L1 protein, human
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Biphenyl Compounds
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CCNB1 protein, human
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CCND2 protein, human
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CDKN1A protein, human
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Cyclin B
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Cyclin B1
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Cyclin D2
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Histones
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Hydroxamic Acids
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins
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Proto-Oncogene Proteins c-bcl-2
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SK-7041
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bcl-X Protein
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trichostatin A
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Histone Deacetylases