Molecular tumour targeting has significantly improved anti-cancer protocols. Still, the addition of molecular targeting to the treatment regime has not led to a curative breakthrough. Combined mammalian target of Rapamycin (mTOR) and histone deacetylase (HDAC) inhibition has been shown not only to enhance anti-tumour potential, but also to prevent resistance development seen under mono-drug the...

Two controversial issues regarding p53 are whether it is involved in apoptosis induction of tumor cells by a histone deacetylase (HDAC) inhibitor and, given that p53 is indeed involved, which genes of acetylated p53 targets are responsible for giving rise to apoptotic death. We, in the present study, first confirmed that some substantial extent of apoptotic cell death was seen when p53-deficien...

Histone deacetylase (HDAC) inhibitors are emerging as a promising new class of cancer therapeutic agents. HDAC inhibitors relieve the deacetylation of histone proteins. However, little is known about the nonhistone targets of HDAC inhibitors and their roles in gene regulation. In this study, we addressed the molecular basis of the down-regulation of the nuclear factor-kappaB (NF-kappaB)-respons...

OBJECTIVES Recent evidence has demonstrated the importance of histone deacetylases (HDAC) in the control of hypertrophic responses in the heart. However, it remains unknown whether inhibition of HDACs plays a role in myocardial ischemia and reperfusion (I/R) injury. We hypothesize that HDAC inhibition triggers preconditioning-like effects against I/R injury. METHODS AND RESULTS Isolated mouse...

Histone deacetylase 1 (HDAC1) is an epigenetic enzyme that regulates key cellular processes, such as cell proliferation, apoptosis, and cell survival, by deacetylating histone substrates. Aberrant expression of HDAC1 is implicated in multiple diseases, including cancer. As a consequence, HDAC inhibitors have emerged as effective anti-cancer drugs. HDAC inhibitor-induced G0/G1 cell-cycle arrest ...

The inhibitory activity of an ω-alkoxy analogue of the HDAC inhibitor, Vorinostat (SAHA), against the 11 isoforms of HDAC is described and evaluated with regard to structural biology information retrieved through computational methods. Preliminary absorption and metabolism studies were performed, which positioned this compound as a potential candidate for further preclinical studies and delinea...

Valproic acid, a histone deacetylase (HDAC) inhibitor, induces the cytochrome P450 2B subfamily. However, the effects of HDAC inhibitors on CYP2B induction are still not fully understood. Nuclear receptor constitutive androstane receptor (CAR) is a key regulator of CYP2B induction. In this study, we investigated the effect of HDAC inhibitors on CAR-mediated CYP2B induction. The expression of CY...

Histone deacetylase (HDAC) inhibitors are new and promising antineoplastic agents. Current methods for monitoring early response rely on invasive biopsies or indirect blood-derived markers. Our goal was to develop a magnetic resonance spectroscopy (MRS)-based method to detect HDAC inhibition. The fluorinated lysine derivative Boc-Lys-(Tfa)-OH (BLT) was investigated as a (19)F MRS molecular mark...

SAHA (vorinostat, Merck) is a famous clinical drug for zinc-containing histone deacetylase (HDAC) targets against cancer and several other human disorders, whose inhibition mechanism (namely the protonation mechanism) upon binding to HDAC has been debated for more than ten years. It is very challenging to verify experimentally and is still controversial theoretically. The popular "Class-depende...