Antitumor activity of SK-7041, a novel histone deacetylase inhibitor, in human lung and breast cancer cells.
BACKGROUND
A class of synthetic histone deacetylase (HDAC) inhibitors, which are hybrids of trichostatin A and MS-275 were previously developed. In this study, the antitumor effects of SK-7041, one of those novel HDAC inhibitors, was evaluated on lung and breast cancer cell lines.


METHODS
Human lung and breast cancer cells, as well as normal human bronchial epithelial (NHBE) cells were treated with SK-7041, and results were compared with those of cells treated with suberoylanilide hydroxamic acid (SAHA).


RESULTS
SK-7041 induced time-dependent histone hyperacetylation and showed more potent cytotoxicity than SAHA in cancer cells. These antiproliferative effects of SK-7041 were due to apoptotic cell death caused by G2/M-phase arrest and to a lesser extent to G1 arrest. Moreover, SK-7041 inhibited cancer cell proliferation more selectively than NHBE cell proliferation.


CONCLUSIONS
These results suggest that SK-7041 may have potential anticancer activity.
Lee
Keun-Wook
KW
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kim
Jee Hyun
JH
Park
Jung-Hyun
JH
Kim
Hwang-Phill
HP
Song
Sang-Hyun
SH
Kim
Sang Gyun
SG
Kim
Tai Young
TY
Jong
Hyun-Soon
HS
Jung
Kyung Hae
KH
Im
Seock-Ah
SA
Kim
Tae-You
TY
Kim
Noe Kyeong
NK
Bang
Yung-Jue
YJ
D000107:Acetylation; D000577:Amides / Q000633:toxicity*; D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000633:toxicity*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000633:toxicity; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D000077337:Vorinostat
D000577:Amides; D017304:Annexin A5; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C497103:SK-7041; D000077337:Vorinostat