Anti-Histone H3 (internal region) polyclonal antibody

Apigenin, a naturally occurring flavonoid, is known to exhibit significant anticancer activity. This study was designed to determine the effects of apigenin on two malignant mesothelioma cell lines, MSTO-211H and H2452, and to explore the underlying mechanism(s). Apigenin significantly inhibited cell viability with a concomitant increase in intracellular reactive oxygen species (ROS) and caused the loss of mitochondrial membrane potential (Delta Psi m), and ATP depletion, resulting in apoptosis and necroptosis in monolayer cell culture. Apigenin upregulated DNA damage response proteins, including the DNA double strand break marker phospho (p)histone H2A.X. and caused a transition delay at the G(2)/M phase of cell cycle. Western blot analysis showed that apigenin treatment upregulated protein levels of cleaved caspase-3, cleaved PARP, p-MLKL, and p-RIP3 along with an increased Bax/Bcl-2 ratio. ATP supplementation restored cell viability and levels of DNA damage-, apoptosis-and necroptosis-related proteins that apigenin caused. In addition, N-acetylcysteine reduced ROS production and improved Delta Psi m loss and cell death that were caused by apigenin. In a 3D spheroid culture model, ROS-dependent necroptosis was found to be a mechanism involved in the anti-cancer activity of apigenin against malignant mesothelioma cells. Taken together, our findings suggest that apigenin can induce ROS-dependent necroptotic cell death due to ATP depletion through mitochondrial dysfunction. This study provides us a possible mechanism underlying why apigenin could be used as a therapeutic candidate for treating malignant mesothelioma.

Histone lysine N-methyltransferase 2D (KMT2D), an important methyltransferase that is involved in the methylation of lysine 4 in histone H3 (H3K4) and related to the development of prostate cancer. Hypermethylation of H3K4 is shown in prostate cancer (PCa). However, KMT2D inhibitors have not yet been developed. This article aims to design small molecule inhibitors targeting KMT2D_SET to prevent PCa cell proliferation and migration. Twenty-four inhibitors were firstly designed according to a virtual screening of computers, and shown different degrees of binding to KMT2D_SET. Compounds 1 and 16 showed high binding affinities to KMT2D, with KD values of 147 +/- 32.9 mu M and 176 +/- 37.9 mu M, respectively. In addition, they exerted strong inhibitory activity against the PCa cell lines PC-3 and DU145, with IC50 values of 1.1 +/- 0.06 mu M, 1.5 +/- 0.06 mu M and 1.8 +/- 0.1 mu M, 2.3 +/- 0.2 mu M, respectively. Furthermore, these two compounds significantly suppressed the migration of PCa cells. (C) 2020 Elsevier Inc. All rights reserved.