PX-12 modulates vorinostat-induced acetylation and methylation marks in CAL 27 cells.

Abstract

Aim: The hypoxic tumor microenvironment (TME) in oral squamous cell carcinoma (OSCC) is primarily regulated by hypoxia-inducible factor-1 alpha (HIF-1α), impacting histone acetylation and methylation, which contribute to drug resistance. Vorinostat, a histone deacetylase inhibitor (HDACi), de-stabilizes HIF-1α, while PX-12, a thioredoxin-1 (Trx-1) inhibitor, prevents HIF-1α accumulation. Combining HDACi with a Trx-1 inhibitor may enhance efficacy and reduce resistance by increasing reactive oxygen species (ROS) in cancer cells. This study examines how PX-12 influences vorinostat-induced histone modifications under hypoxia in the OSCC cell line CAL 27 using mass spectrometry.

Materials and methods: The OSCC cell line CAL 27 was used to assess histone post-translational modifications induced by PX-12 and Vorinostat under hypoxic conditions through mass spectrometry.

Results: The proteomic analysis (ProteomeXchange identifier PXD053244) revealed several crucial histone marks, such as H3K4me1, H3K9ac, H3K9me, H3K14ac, H3K27me, H3K36me, H4K12Ac, and H4K16ac. Along with site-specific histone modifications, exposure of cells to vorinostat and PX-12 alone or in combination affects the global acetylation and methylation levels under hypoxia.

Conclusion: Mass spectrometry-based proteomics highlighted the impact of vorinostat and PX-12 on histone acetylation and methylation, offering valuable insights into the epigenetic mechanisms in OSCC and paving a way for epigenetic-based oral cancer therapeutics.