Valproic acid inhibits proliferation of HER2-expressing breast cancer cells by inducing cell cycle arrest and apoptosis through Hsp70 acetylation

摘要: Breast cancer encompasses a heterogeneous group of diseases at the molecular level. It is known that chemosensitivity breast depends on its subtype. We investigated growth inhibitory effect valproic acid (VPA), histone deacetylase (HDAC) inhibitor, and mechanism this inhibition four cell lines with different subtypes. The VPA in was investigated. alteration levels p21 WAF1, cleaved caspase-3, acetylated Heat shock protein (Hsp) 90, Hsp70, α-tubulin by examined VPA-sensitive, human epidermal receptor 2 (HER2)-overexpressing SKBR3 cells. dependent dose exposure time VPA. HER2-overexpressing line inhibited to much greater degree than other studied. In line, upregulated expression WAF1 caspase-3 early phase. markedly increased Hsp70 acetylation time-dependent manner but did not increase Hsp90 acetylation. Our data demonstrated proliferation induced cycle arrest apoptosis This anti-proliferation might be direct function as an HDAC inhibitor. propose alternative whereby disrupts leads downregulation client proteins, including HER2 indirect VPA, sense non-histone proteins are acetylated.