trichostatin A (VTR-297)

Pharmacological restoration of histone acetylation with the HDAC inhibitor Trichostatin A (TSA) effectively suppressed tumor growth. Collectively, our findings identify KMT2C as a key epigenetic regulator linking promoter histone acetylation, NF2-Hippo pathway activity, and ferroptosis susceptibility. These results provide mechanistic insights into high-grade meningioma progression and highlight ferroptosis induction and epigenetic modulation as promising therapeutic strategies for NF2-wild-type, KMT2C-deficient meningiomas.

P2, N=50, Active, not recruiting, Vanda Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: May 2026 --> Sep 2026 | Trial primary completion date: Mar 2026 --> Sep 2026

Consistently, pharmacological agents-Trichostatin A as a histone deacetylase inhibitor and chaetocin as a histone methyltransferase inhibitor-induced nucleosome scattering and converted U2OS cells into iTS cells, whose conditioned media exerted tumor-suppressive effects. Our findings highlight nucleosome clustering as a key epigenetic feature responsive to both biophysical and chemical cues, underscoring its role in microscale chromatin remodeling and reprogramming of the tumor microenvironment.

To functionally validate these findings, we treated OSCC cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (DAC) and histone deacetylase inhibitors trichostatin A (TSA) and valproic acid (VPA). The triple-drug combination treatment resulted in the most robust reactivation of MAGED4 expression, correlating with promoter DNA demethylation and enhanced acetylation of H3K9 and H3K27 at the MAGED4 promoter. Our findings elucidate critical epigenetic mechanisms contributing to MAGED4 heterogeneity in OSCC and highlight the potential of combination epigenetic therapies to reverse this heterogeneity, thereby providing a foundation for exploring such approaches to improve immunotherapeutic outcomes.

Although previous research focuses on the direct impact of TSA on tumor cells, in our study, we exclusively highlight TSA ability to reprogram the immune cells epigenetically in a more inflammatory tumor-reactive phenotype. The findings justify the possibility of TSA as an epigenetic adjunct of low toxicity in immuno-oncology and form a basis to continue in vivo and translational study in CRC immunotherapy.

Drug screening identified 22 potential therapeutic compounds, with trichostatin A showing optimal binding affinity. These findings establish TMOD2 and DOCK4 as novel biomarkers linking GM dysbiosis to CRA development, opening new avenues for microbiome-targeted early intervention strategies.

Therefore, we investigated the interactions between the ligands quercetin (QUE), isoquercetin (ISO), catechin gallate (CG), and trichostatin A (TSA) with SIRT6, using computational methods from the perspective of molecular modeling through the Molecular Fractionation with Caps Conjugates (MFCC) technique and according to the calculation parameters of Density Functional Theory (DFT)...In addition, residues such as PRO62, MET136, MET157, and VAL115 stand out as key components of the protein active site. These findings offer strategic insights into the molecular mechanisms underlying the binding of the studied ligands to SIRT6, providing a deep understanding of their affinity and pharmacological potential.

These in vivo findings indicate that efficient tumor targeting by MSCs is crucial for achieving therapeutic efficacy, especially in TRAIL-resistant tumors. Overall, our results demonstrate that co-treatment with TSA enhances the antitumor effect of TRAIL-expressing MSCs, offering a potential strategy to overcome TRAIL resistance and improve MSC-based cancer therapies.

Intriguingly, administration of the histone deacetylase inhibitor trichostatin A resulted in the upregulation of CYP3A5 expression...Because ESCC develops, CYP3A5 suppression promotes tumor metastasis and invasion. CYP3A5 is a potential biomarker and therapeutic target for ESCC.

Our study reveals a previously unrecognized role of Trunc-APC in dampening tumor-intrinsic innate immunity and suggests that co-targeting Trunc-APC with epigenetic therapy may offer a promising strategy to enhance anti-tumor immune responses in CRC.

Moreover, pharmacological inhibition of HDAC with Trichostatin A (TSA) suppressed both HDAC6 and BNIP3 expression, decreased autophagic activity, and reduced lung tumor formation in a KRASG12D+/P53loxP/loxP transgenic mouse model. Collectively, these results reveal a novel HDAC6-HIF-1α-BNIP3 axis that governs autophagy in lung cancer and underscore the potential of HDAC6 as a therapeutic target for modulating autophagy and inhibiting lung tumor progression.

Pharmacological inhibition of deacetylases by Trichostatin A (TSA) restored H4K16ac, suppressed autophagy, and exacerbated apoptosis. Similarly, Sirtuin 1 (SIRT1) knockdown upregulated H4K16ac, inhibited autophagic flux, and promoted apoptosis via the Bax/Bcl-2/caspase-3 pathway. These findings reveal that H4K16ac downregulation post-SCI enhances autophagy as a protective response, while its restoration via SIRT1 inhibition disrupts this balance, aggravating neuronal apoptosis.