Histone deacetylase inhibitor, apicidin, inhibits human ovarian cancer cell migration via class II histone deacetylase 4 silencing |
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Authors: | Mee Young Ahn Dong O Kang Yong Jin Na Sungpil Yoon Whan Soo Choi Keun Wook Kang Hae Young Chung Jee H Jung Do Sik Min Hyung Sik Kim |
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Affiliation: | Department of Oral & Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon 302-120, Republic of Korea. |
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Abstract: | 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. |
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Keywords: | HDAC inhibitor Ovarian cancer Migration Apicidin HDAC4 |
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