PX-12 Modulates Vorinostat-induced acetylation and methylation marks in CAL 27 cells

ABSTRACT: The hypoxic tumor microenvironment (TME) is a common hallmark of solid cancers, including oral squamous cell carcinoma (OSCC). Hypoxia is predominantly regulated by the hypoxia-inducible factor-1 alpha (HIF-1α) and can alter the histone acetylation and methylation profile involved in drug resistance and possible therapeutic options for solid cancer. Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase inhibitor (HDACi) that targets HIF-1α stability, whereas PX-12 (1-methylpropyl 2-imidazolyl disulfide) is a thioredoxin-1 (Trx-1) inhibitor that prevents HIF-1α accumulation. Although HDACi are efficient in cancer treatment, they are accompanied by several adverse effects and increased resistance. This can be averted by combining HDACi with a Trx-1 inhibitor, as both inhibitors are connected by interlinked inhibitory pathways. HDACi inhibit Trx-1, leading to elevated reactive oxygen species (ROS) formation and death in cancerous cells; consequently, utilizing a Trx-1 inhibitor can boost the efficacy of HDACi. Previously, we investigated a synergistic interaction between vorinostat and PX-12 in an oral squamous carcinoma (OSCC) cell line under hypoxia. Here, we report to determine the effect of both inhibitors on histone acetylation and methylation expression levels under hypoxia in the CAL 27 cell line using mass spectrometry. We found several crucial histone marks, such as H3K4me1, H3K9ac, H3K9me, H3K14ac, H3K27me, H3K36me, H4K12Ac, and H4K16ac. The global analysis for histone acetylation and methylation and on specific residue shows their expression level was altered differentially by individual and combined inhibitor treatment. Our results provide an implication to investigate the underlying epigenetic mechanisms of histone acetylation and methylation levels in oral squamous cell carcinoma for a better understanding of developing drugs for cancer therapy.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Oral Squamous Cell Carcinoma Cell

SUBMITTER: Simone Sidoli  

LAB HEAD: Simone Sidoli

PROVIDER: PXD053244 | Pride | 2025-05-07

REPOSITORIES: Pride