Abstract
Suberoylanilide hydroxamic acid (SAHA), a pan HDAC inhibitor, has been approved by the Food and Drug Administration (FDA) to treat cutaneous T cell lymphoma (CTCL). Nevertheless, the mechanisms underlying the therapeutic effects of SAHA on tumors are yet not fully understood. Protein phosphorylation is one of the most important means to regulate key biological processes (BPs), such as cell division, growth, migration, differentiation, and intercellular communication. Thus, investigation on the impacts of SAHA treatment on global cellular phosphorylation covering major signaling pathways deepens our understanding on its anti-tumor mechanisms. Here we comprehensively identified and quantified protein phosphorylation for the first time in nasopharyngeal carcinoma (NPC) cells upon SAHA treatment by combining tandem mass tags (TMTs)-based quantitative proteomics and titanium dioxide (TiO2)-based phosphopeptide enrichment. In total, 7,430 phosphorylation sites on 2,456 phosphoproteins were identified in the NPC cell line 5-8F, of which 1,176 phosphorylation sites on 528 phosphoproteins were significantly elevated upon SAHA treatment. Gene ontology (GO) analysis showed that SAHA influenced several BPs, including mRNA/DNA processing and cell cycle. Furthermore, signaling pathway analysis and immunoblotting demonstrated that SAHA activated tumor suppressors like p53 and Rb1 via phosphorylation and promoted cell apoptosis in NPC cells but inactivated energetic pathways such as AMPK signaling. Overall, our study indicated that SAHA exerted anti-tumor roles in NPC cells, which may serve as novel therapeutic for NPC patients.
Highlights
Nasopharyngeal carcinoma, as a common type of head and neck cancer, has a much higher incidence in Southern China and Southeast Asia, where the annual incidence is about 30 cases per 100,000 persons, in contrast to fewer than one case per 100,000 persons in the United States and Europe (Chang and Adami, 2006; Cao et al, 2011)
Combining quantitative phosphoproteomics and bioinformatic analysis, we demonstrated that suberoylanilide hydroxamic acid (SAHA) treatment altered phosphorylation in key signaling pathways in nasopharyngeal carcinoma (NPC) cells
We indicated that SAHA inhibits proliferation and induces apoptosis in NPC cells
Summary
Nasopharyngeal carcinoma, as a common type of head and neck cancer, has a much higher incidence in Southern China and Southeast Asia, where the annual incidence is about 30 cases per 100,000 persons, in contrast to fewer than one case per 100,000 persons in the United States and Europe (Chang and Adami, 2006; Cao et al, 2011). Histone deacetylases play key roles in regulating chromatin remodeling, the gene expressions of which they regulate epigenetically by turning down histone lysine acetylation in various pathophysiological conditions (Shahbazian and Grunstein, 2007). Both HDACs and histone lysine acetylation are involved in tumorigenesis, and inhibition of HDACs by specific inhibitors has emerged as an effective anti-tumor strategy (Wagner et al, 2010).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
