SK-7041, a new histone deacetylase inhibitor, induces G2-M cell cycle arrest and apoptosis in pancreatic cancer cell lines.
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.
Ryu
Ji Kon
JK
Departments of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungun-dong, Chongno-gu, Seoul 110-744, South Korea.
Lee
Woo Jin
WJ
Lee
Kwang Hyuck
KH
Hwang
Jin-Hyeok
JH
Kim
Yong-Tae
YT
Yoon
Yong Bum
YB
Kim
Chung Yong
CY
D000577:Amides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002455:Cell Division; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D056742:Cyclin D2; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016195:G2 Phase; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D000577:Amides; D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D001713:Biphenyl Compounds; C534699:CCNB1 protein, human; C080336:CCND2 protein, human; C493956:CDKN1A protein, human; D019926:Cyclin B; D056744:Cyclin B1; D056742:Cyclin D2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C497103:SK-7041; D051020:bcl-X Protein; C012589:trichostatin A; D006655:Histone Deacetylases