Histone deacetylase inhibitors require caspase activity to induce apoptosis in lung and prostate carcinoma cells.

Histone deacetylase inhibitors (HDIs) are a promising new class of antineoplastic agents with the capacity to induce growth arrest and/or apoptosis of cancer cells. However, their precise mechanism of action is uncertain; particularly, the role of caspases in the apoptotic response to HDIs is controversial. Here, we show that the HDIs explored, suberoylanilide hydroxamic acid, sodium butyrate and trichostatin A, activated caspase-3 in A549 and PC-3 carcinoma cells. Additionally, the poly-caspase inhibitor z-VAD-fmk prevented HDI-induced apoptosis, as judged by determining mitochondrial membrane potential and by quantifying internucleosomal DNA fragmentation. Importantly, z-VAD-fmk also significantly inhibited HDI-elicited cell death, as assessed by measuring propidium iodide uptake. As an accessory finding, with the inhibition of caspases, a HDI-induced G2-M arrest became evident. Taken together, these results provide evidence that HDIs require activated caspases to induce apoptosis of carcinoma cells.

Role of oxygen vacancy and Fe-O-Fe bond angle in compositional, magnetic, and dielectric relaxation on Eu-substituted BiFeO(3) nanoparticles.

The influence of oxygen vacancies on the dielectric relaxation behavior of pure and Eu-substituted BiFeO3 nanoparticles synthesized by a sol-gel technique has been studied using impedance spectroscopy in the temperature range of 90 °C to 180 °C. The electric relaxation time and activation energy of the oxygen vacancies can be calculated from the Arrhenius equation, and found to be 1.26 eV and 1.76 eV for pure and Eu-substituted BiFeO3, respectively. Substitution induces structural disorder and changes in the Fe-O-Fe bond angle, leading to alteration of the magnetic properties, observed from magnetic studies and evaluated using Rietveld refinement of the XRD patterns. X-ray photoelectron spectroscopy (XPS) confirms the shifting of the binding energy of the Bi 4f orbital, establishing Eu substitution at the Bi site. Calculation of the area under the Fe(2+)/Fe(3+) (2p) and O (1s) XPS spectra gives approximate values of the oxygen vacancies.