sk-7041 and Pancreatic-Neoplasms

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.

Topics: Amides; Antineoplastic Agents; Apoptosis; bcl-X Protein; Biphenyl Compounds; Cell Division; Cell Line, Tumor; Cell Proliferation; Cyclin B; Cyclin B1; Cyclin D2; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Dose-Response Relationship, Drug; Enzyme Inhibitors; G2 Phase; Histone Deacetylase Inhibitors; Histone Deacetylases; Histones; Humans; Hydroxamic Acids; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Proteins; Pancreatic Neoplasms; Proto-Oncogene Proteins c-bcl-2