Aqueous extract induces cell apoptosis in human hepatocellular carcinoma cells.

Treatment of advanced hepatocellular carcinoma (HCC) has exhibited a poor overall survival rate of only six to ten months, and the urgency of the development of more effective novel agents is ever present. In this line of research, we aimed to investigate the effects and inhibitive mechanisms of aqueous leaf extract (OGE), the extract of , which is commonly used as a therapeutic herb for its numerous pharmacological properties, on malignant HCC cells. Our results showed that OGE decreased the cell viability of HCC SK-Hep1 and HA22T cells in a dose-dependent manner (from 400 to 800 µg/mL), while there is little effect on Chang liver cells.

MZF-1/Elk-1/PKCα is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma.

Protein kinase C alpha (PKCα) is a key signaling molecule in human cancer development. As a therapeutic strategy, targeting PKCα is difficult because the molecule is ubiquitously expressed in non-malignant cells. PKCα is regulated by the cooperative interaction of the transcription factors myeloid zinc finger 1 (MZF-1) and Ets-like protein-1 (Elk-1) in human cancer cells.

MZF-1/Elk-1 Complex Binds to Protein Kinase Cα Promoter and Is Involved in Hepatocellular Carcinoma.

In this study, the molecular mechanism of protein kinase C alpha (PKCα) gene regulation in hepatocellular carcinoma (HCC) involving Ets-like protein-1 (Elk-1) and myeloid zinc finger-1 (MZF-1) was investigated. The luciferase reporter assay results revealed that the presence of both MZF-1 and Elk-1 significantly contributed to the upregulation of PKCα gene transcription activity, and the transcriptional activity decreased when the transfection included a DNA-binding-deficient (∆DBD) gene vector of either MZF-1 or Elk-1 DNA-binding deficiency (MZF-1∆DBD or Elk-1∆DBD), thereby indicating that the enhanced expression of PKCα was caused by the binding of MZF-1 and/or Elk-1 with the PKCα promoter. We investigated MZF-1 and Elk-1 to determine whether they bind to each other.

Lipopolysaccharide-stimulated leukocytes contribute to platelet aggregative dysfunction, which is attenuated by catalase in rats.

Endotoxemia causes several hematological dysfunctions, including platelet degranulation or disseminated intravascular coagulation, which lead to thrombotic and hemorrhagic events. Here, we tested the hypothesis that bacterial lipopolysaccharide (LPS)-stimulated leukocytes contribute to platelet aggregative dysfunction, and this function is attenuated by antioxidants. Platelet-rich plasma (PRP) was prepared from whole blood of normal and endotoxemic rats.

The protection of hepatocyte cells from the effects of oxidative stress by treatment with vitamin E in conjunction with DTT.

We investigated the effect of vitamin E on membrane protein thiols under oxidative stress, which we induced by treating hepatocytes with tert-butyl hydroperoxide (TBH) for 60 mins. Those cells which we pretreated with vitamin E formed fewer blebs (22.3% compared to 60.

Effect of carbon dioxide on pulmonary vascular tone at various pulmonary arterial pressure levels induced by endothelin-1.

There have been contradictory reports suggesting that CO(2) may constrict, dilate, or have no effect on pulmonary vessels. Permissive hypercapnia has become a widely adopted ventilatory technique used to avoid ventilator-induced lung injury, particularly in patients with acute respiratory distress syndrome (ARDS). On the other hand, respiratory alkalosis produced by mechanically induced hyperventilation is the mainstay of treatment for newborn infants with persistent pulmonary hypertension.

The activation of matrix metalloproteinase-2 induced by protein kinase C alpha in decidualization.

This study investigated the protein kinase C (PKC) and matrix metalloproteinase-2 (MMP-2) in the development of deciduomata in pseudo-pregnant and pregnant rats. The results showed that the expression of MMP-2 was significantly increased from day 2 to day 5 in pseudo-pregnancy and from day 7 to day 9 in pregnancy. To further investigate the correlation between MMP-2 and protein kinase C alpha (PKC alpha), the expression of MMP-2 in the 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated organotypic culture of decidual tissue was determined.

Immunochemical localization of protein kinase Calpha in the biopsies of human hepatocellular carcinoma.

The purpose of this study was to elucidate the protein kinase C (PKC) alpha distribution in human hepatocellular carcinoma (HCC). The histoimmunopathologic technique was used to determine the localization and expression of PKCalpha in HCC biopsies. The HCC tissues were classified as cytosolic type (PKCalpha deposited in the cytoplasm in > 50% of cells) and membranous type for the remaining ones.

Inhibition of intermediate-conductance Ca2+-activated K+ channel and cytoprotective properties of 4-piperidinomethyl-2-isopropyl-5-methylphenol.

The ionic mechanisms and cytoprotective activities of 4-piperidinomethyl-2-isopropyl-5-methylphenol (THPI), an analogue of thymol, were investigated in HL-60 granulocytes and in human erythrocytes, respectively. THPI inhibited K+ outward current (I(K)) in a concentration-dependent manner in HL-60 leukocytes, with an IC50 value of 4 microM. Neither iberiotoxin (200 nM) nor paxilline (1 microM) suppressed the amplitude of I(K), whereas clotrimazole (5 microM) significantly inhibited it.

Overexpression of anion exchanger 2 in human hepatocellular carcinoma.

To compare gene expression patterns between the poorly-differentiated (HA22T/VGH) and well-differentiated (HepG2) hepatocellular carcinoma cells, messenger RNA was isolated form both kinds of cells and subjected to differential displays reversing transcriptase-polymerase chain reaction (DDRT-PCR) technology. Gene fragments showing difference in the expression were recovered, reamplified, cloned and sequenced. Anion exchanger 2 (AE2), an isoform of band 3 protein, was identified and chosen for further characterization.

Expression of protein kinase C alpha in biopsies and surgical specimens of human hepatocellular carcinoma.

Variations in the activity of protein kinase C (PKC) have been observed in different types of tumors. Although these inconsistent findings may be attributed to the alterations of individual PKC isoforms, the effects of general anesthetic may not be neglected. In this study, biopsies and surgical specimens were obtained from patients with HCC, and the levels of PKCalpha were analyzed by immunohistochemistry.

PKCalpha expression regulated by Elk-1 and MZF-1 in human HCC cells.

Our previous study found that PKCalpha was highly expressed in the poor-differentiated human HCC cells and associated with cell migration and invasion. In this study, we further investigated the gene regulation of this enzyme. We showed that PKCalpha expression enhancement in the poor-differentiated human HCC cells was found neither by DNA amplification nor by increasing mRNA stability using differential PCR and mRNA decay assays.

17beta-estradiol reduces cardiac hypertrophy mediated through the up-regulation of PI3K/Akt and the suppression of calcineurin/NF-AT3 signaling pathways in rats.

This study was designed to determine the effects of 17beta-estradiol (E2) in overcoming the cardiac over-loading and cardiac fibrosis in rats. E2 (100 ng/kg) or oil was applied in female Sprague-Dawley rats with or without bilateral ovariectomy and with or without coarctation of the abdominal aorta after 4 or 8 days. By post-operative day 4, the heart weight, the left ventricular weight, the latent form of MMP-2 in rat hearts with or without the ovary intact had significantly increased while these changes were reversed after E2 treatment.

Augmented release of matrix metalloproteinase-9 by PKC activation in organotypic cultures of human breast cancer and adjacent normal breast tissue and fibroadenoma.

The organotypic culture technique and quantitative gelatin zymography were used to determine the expression of matrix metalloproteinase (MMP)-9 and MMP-2 in human breast cancer and adjacent normal breast tissue and fibroadenoma. MMP-9 and MMP2 were constitutively expressed in all cultures. The release of these two enzymes in breast cancer was higher than that in adjacent normal breast tissue and fibroadenoma.