SAHA Treatment Reveals the Link between Histone Lysine Acetylation and Proteome in Nonsmall Cell Lung Cancer A549 Cells

Suberoylanilide
hydroxamic acid (SAHA) is a well-known pan HDAC inhibitor, and its
clinical application (Vorinostat) has been demonstrated to treat nonsmall
cell lung cancer (NSCLS). Nevertheless, the impact of SAHA treatment
on histone lysine acetylation and proteome in NSCLS cells still need
further elucidate. In NSCLS A549 cells, by using stable isotope labeling
for cell culture (SILAC)-based quantitative proteomics, biochemistry
assay, and bioinformatic analysis, here we for the first time comprehensively
identified and quantified histone lysine acetylation in A549 cells
toward SAHA treatment. Despite the fact that SAHA treatment significantly
increased histone lysine acetylation in specific sites, unexpectedly,
some important “histone markers” showed markedly decreased
acetylation level. Further quantitative proteome studies showed that
among totally quantifiable 2818 nonredundant proteins, 1355 proteins
were with increased level and 1463 with decreased level in response
to SAHA treatment. Bioinformatic analysis further revealed that those
quantifiable proteins were mainly involved in multiple biological
functions and metabolic and enzyme-regulated pathways as well as protein
complexes. By establishing the link between histone modification and
whole proteome in response to SAHA treatment in NSCLS cells, this
study therefore may deepen our understanding of HDAC inhibitor-mediated
cancer therapeutics.