title: VPA inhibits breast cancer cell migration by specifically targeting HDAC2 and down-regulating Survivin.
abstract: Cell migration plays major roles in human breast cancer-related death, but the molecular mechanisms remain unclear. Valproic acid (VPA) is a broad-spectrum inhibitor of class I and II histone deacetylases and shows great anticancer activity in a variety of human cancers including breast cancer. In this study, we found that VPA significantly inhibited cell migration but not proliferation of human breast cancer MDA-MB-231 cells. Mechanistic studies found that VPA significantly inhibited the expression of Survivin. Knockdown of Survivin could obviously inhibited cell migration, while over-expression of Survivin markedly rescued the inhibition of VPA on cell migration. Further studies found that knockdown of HDAC2 completely mimicked the effects of VPA on Survivin and cell migration, and over-expression of Survivin could also rescue the effects of HDAC2 knockdown on cell migration. Collectively, these results indicated that HDAC2 may be the specific target of VPA in breast cancer cells, and specific inhibition of HDAC2, especially by small molecular chemicals may lead to less side-effects and provide a better strategy than VPA application for human breast cancer treatment.
authors.affiliation: Clinical and Translational Research Center at Shanghai First Maternity & Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Guiying
authors.initials: G
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Chenlin
authors.initials: C
authors.lastname: Song
authors.forename: Ye
authors.initials: Y
authors.lastname: Leng
authors.forename: Xinhua
authors.initials: X
authors.lastname: Wang
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D000077022:Survivin; D014635:Valproic Acid / Q000494:pharmacology*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D014635:Valproic Acid; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2