Oxymatrine is one of the primary natural compounds extracted from the Sophora flavescens, and has been reported to exhibit numerous pharmacological properties including cancer‑preventive and anti‑cancer effects, however the mechanisms as to how oxymatrine exhibits anti‑proliferative activity in non‑small cell lung carcinoma cells remains uncertain. The present study aimed to explore the mechanism of its anti‑cancer effect, and whether it is due to apoptosis induction and anti‑migration in the A549 lung cancer cell line. Detection of morphological alterations, MTT analysis, Hoechst/propidium iodide dual staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assays verified that oxymatrine induced A549 cell apoptosis. The caspase pan‑inhibitor z‑VAD‑FMK resulted in disappearance of oxymatrine‑elicited nuclei fragmentation via Hoechst 33342 staining. JC‑1 staining demonstrated a decrease in mitochondrial membrane potential which further verified the induction of apoptosis by oxymatrine. The caspase‑3, 8 and 9 activities of oxymatrine‑treated cells were activated, which suggested that extrinsic and intrinsic apoptotic pathways were involved in the anti‑proliferative effects of oxymatrine in A549 cells. Furthermore, the wound healing assay verified the anti‑migratory effects of oxymatrine in A549 cells.

Excessive and abnormal vessel growth plays a critical role in the pathogenesis of many diseases, such as cancer. Angiogenesis is one of the hallmarks of cancer growth, invasion, and metastasis. Discovery of novel antiangiogenic agents would provide new insights into the mechanisms of angiogenesis, as well as potential drugs for cancer treatment. In the present study, we investigated the antiangiogenic activity of a series of monocarbonyl analogs of curcumin synthesized previously in our lab. We found that curcumin analog A2 displayed the full potential to be developed as a novel antiangiogenic agent. Curcumin analog A2 at and above 20 μM dramatically inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, new microvessels sprouting from the rat aortic rings ex vivo and newly formed microvessels in chicken chorioallantoic membranes (CAMs) and Matrigel plus in vivo. We further demonstrated that curcumin analog A2 exerted its antiangiogenic activity mainly through inducing endothelial cell death via elevating NADH/NADPH oxidase-derived ROS. Curcumin analog A2 at the antiangiogenic concentrations also triggered autophagy in HUVECs, but this process is neither a prerequisite for toxicity, leading to the cell death nor a protective response against the toxicity of curcumin analog A2. In conclusion, we demonstrate for the first time the potent antiangiogenic activity of the monocarbonyl curcumin analog A2, which could serve as a promising potential therapeutic agent for the prevention and treatment angiogenesis-related diseases, such as cancer.

ABSTRACT. This study aimed to investigate cytosine methylation profiles in different tobacco (Nicotiana tabacum) cultivars grown in China. Methylationsensitive amplified polymorphism was used to analyze genome-wide global methylation profiles in four tobacco cultivars (Yunyan 85, NC89, K326, and Yunyan 87). Amplicons with methylated C motifs were cloned by reamplified polymerase chain reaction, sequenced, and analyzed. The results show that geographical location had a greater effect on methylation patterns in the tobacco genome than did sampling time. Analysis of the CG dinucleotide distribution in methylation-sensitive polymorphic restriction fragments suggested that a CpG dinucleotide cluster-enriched area is a possible site of cytosine methylation in the tobacco genome. The sequence alignments of the Nia1 gene (that encodes nitrate reductase) in Yunyan 87 in different regions indicate that a C-T transition might be responsible for the (2015) tobacco phenotype. T-C nucleotide replacement might also be responsible for the tobacco phenotype and may be influenced by geographical location.

Heavy metals in the environment are one of the major limiting factors affecting plant growth and development. However, the mechanisms of the heavy metal-induced physiological processes remain to be fully dissected. Here, we explored that SRO1 can physically interact with Glutathione Peroxidase 3 (GPX3) in Arabidopsis. Under Hg treatment, similar to the sro1, the growth of the gpx3/sro1 was repressed more seriously and the number of true leaves was more reduced and etiolated than that of the wild type and gpx3 plants. The electrolyte leakage rates showed that cell membrane integrity in gpx3/sro1 was damaged more severely than in the wild type and gpx3 mutant. The Real-time PCR results have shown that the expression of the APX1 and CAT3 was reduced under mercury stress in the sro1 and sro1/gpx3. Our results suggested that the combination of the SRO1 and GPX3 may be contributed to plant response to mercury stress by regulating ROS intracellular oxidative homeostasis.

The heart is the most fatty acid-dependent muscle in mammals, but flight muscles of birds and insects encounter even higher rates of fatty acid oxidation. The amount of the muscle fatty acid binding protein (H-FABP) found in these muscle reflects their metabolic activities, and increased fatty acid metabolism in endurance exercise increases FABP expression further. We have studied the mechanism of fatty acid-dependent expression of the H-FABP gene, taking advantage of the comparative analysis of gene control in functionally related, but evolutionary distant animal systems, i.e., rat heart and locust flight muscle. Luciferase reporter genes with a full-length promoter ( approximately 1 kb) from either the locust or the rat were strongly expressed in L6 myoblasts, and the expression of both constructs was markedly increased by fatty acid treatment. Because of its stronger induction by fatty acids and the absence of other vertebrate transcription factor binding sites, the locust promoter was advantageous for the identification of a fatty acid response element (FARE), an inverted repeat of a hexanucleotide half site reminiscent of steroid hormone receptor binding sites (IR-3). All mammalian H-FABP promoters contain similar sequences, however in reverse orientation (everted repeats, ER-3). Deletion of the FARE eliminated the fatty acid inducibility completely for the locust promoter, but only partly for its mammalian analogue, perhaps because of additional factors or more complex interactions. In gel shift studies, the element binds nuclear proteins from both rat cells and locust flight muscle, further attesting to the far-reaching conservation of this mechanism. Two individual proteins bind to the element, with full binding requiring the presence of free fatty acid. Antibodies to PPARs failed to induce a supershift of the protein-DNA complex, indicating that other transcription factors are responsible for the fatty acid-mediated induction of gene expression of H-FABP.