Histone deacetylase inhibitor, apicidin, inhibits human ovarian cancer cell migration via class II histone deacetylase 4 silencing.
This study examined the molecular mechanisms of apicidin in the modulation of human ovarian cancer SKOV-3 cells invasion and migration. Apicidin markedly decreased histone deacetylase 4 (HDAC4) expression and blocked cell migration and invasion. Cell migration was inhibited via down-regulation of matrix metalloproteinase-2 (MMP-2) and up-regulation of RECK in the HDAC4-blocked SKOV-3 cells. Apicidin significantly suppressed the binding of HDAC4 to Sp1 binding elements of the RECK promoter via repression of HDAC4. In an in vivo model, apicidin suppressed the growth of transplanted SKOV-3 cells by down-regulating HDAC4 and MMP-2. Apicidin may potentially be used as an anti-cancer agent for inhibition of cancer cell migration and invasion through the repression of MMP-2 which is related to the reduction of HDAC4.
Department of Oral & Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Institute, Daejeon Dental Hospital, Wonkwang University, Republic of Korea.
Mee Young
MY
Ahn
Dong O
DO
Kang
Yong Jin
YJ
Na
Sungpil
S
Yoon
Whan Soo
WS
Choi
Keun Wook
KW
Kang
Hae Young
HY
Chung
Jee H
JH
Jung
Do Sik
do S
Min
Hyung Sik
HS
Kim
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D002465:Cell Movement / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D010051:Ovarian Neoplasms / Q000473:pathology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*
D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D056572:Histone Deacetylase Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D009363:Neoplasm Proteins; D010456:Peptides, Cyclic; C115460:RECK protein, human; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C102351:apicidin; D020778:Matrix Metalloproteinase 2; C400300:HDAC4 protein, human; D006655:Histone Deacetylases