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Objectives Strategies that induce apoptosis of malignant cells are recognized as effective cancer treatments. This study evaluated the apoptosis-inducing ability of momordin Ic against cholangiocarcinoma (CCA) cells and the respective underlying mechanisms. Methods Quantification of apoptotic cells was performed using Annexin V/7-AAD double dye staining followed by flow cytometry. The effect of momordin Ic on the expression of epidermal growth factor receptor (EGFR) and its downstream signalling molecules was determined via Western blot analysis. The RT2 Profiler PCR Array was used to determine the expression of cell death-associated genes. Expression levels of apoptosis-related proteins were examined using an apoptosis antibody array. Key findings Momordin Ic potently limited the ability of CCA cells to thrive by promoting apoptotic cell death. This apoptosis-inducing activity was accompanied with suppression of expression of EGFR, p-EGFR, c-Myc and other downstream EGFR signalling-related molecules. Additional molecular analyses demonstrated that momordin Ic modified the expression profile of cell death-associated genes in CCA cells. Moreover, significant upregulation of apoptosis-activating proteins and downregulation of apoptosis-inhibiting protein were also observed after exposure to momordin Ic. Conclusions These results suggest that momordin Ic has a potential therapeutic opportunity for CCA treatment by acting as an EGFR suppressant. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA), epithelial bile duct cancer, is deadly cancer with a very poor prognosis and standard anticancer drugs strategy remains poor and unfavorable outcomes. Objectives: In this study, we examined how Oroxylum indicum leaf extract in combination with gemcitabine (anticancer drug) affects the viability, apoptosis, and migration of CCA cells. Materials and Methods: Two CCA cells, KKU-100 and KKU-M452, were incubated with O. indicum or gemcitabine or in combination for 24-72 hr and these effects were explored by using the sulforhodamine B, colony formation, cell cycle arrest, ROS formation, mitochondrial function, migration, and Western blot analysis. Results: O. indicum expressively suppressed the growth of both CCA cells at 72 hr with IC50 values were 9.88 ± 1.36 and 8.56 ± 1.02 μg/mL for KKU-100 and KKU-M452 cells, with the number of cells were decreased by dose-dependent manner. Further, the extract caused the reduction of colony formation and then suppressed the cells at G0/G1 phase for KKU-100 and S to G2/M phase for KKU-M452 cells. At 250 μg/mL, two CCA cells generated ROS formation along with decreasing mitochondrial function and then led to induce cancer cells apoptosis. Furthermore, O. indicum extract inhibited CCA cell migration via decreasing MMP-9 expression levels. The mechanism of its action was significant suppressed EGFR and caspase 3 levels. Combination group of O. indicum plus gemcitabine found that O. indicum potentiated gemcitabine to inhibit cell viability, induce apoptosis, increase ROS formation, decrease mitochondrial function, and suppress EGFR expression. Conclusion: O. indicum leaf extracts with potentiation of gemcitabine can reduce CCA cell growth, induce apoptosis, and cell migration through decreasing EGFR and caspase 3 expression. O. indicum could be useful for enhancing the activity of anticancer drugs displayed to prevent or treat CCA. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Moringa oleifera leaf extract on angiogenesis and inflammatory process in a rat model of streptozotocin-induced diabetic nephropathy. Methods: Four weeks after a single injection of 50 mg/kg streptozotocin, rats were treated with 100 or 200 mg/kg/day Moringa oleifera leaf extract, 1 mg/kg/day dapagliflozin, or a combination of Moringa oleifera leaf extract and dapagliflozin for further eight weeks. Renal function, kidney histology, and gene expression were evaluated at the end of the experiment. Results: Renal function of diabetic rats was significantly impaired as evidenced by increased blood urea nitrogen, albuminuria, 24-h proteinuria, and high creatinine clearance which indicated glomerular hyperfiltration. In addition, diabetic rats showed an increase in gene expressions of vascular endothelial growth factor-A (VEGF-A), angiopoietin-2 (Ang2), the Ang2/Ang1 ratio, tumor necrosis factor-α, interleukin-1β and monocyte chemoattractant protein-1. Immunohistochemical staining demonstrated a significant increase in the density of glycoprotein CD34. Moringa oleifera leaf extract markedly improved all renal dysfunction markers and modulated the upregulated expression of angiogenic factors and inflammatory genes. Conclusions: Moringa oleifera leaf extract could suppress abnormal angiogenesis and inflammatory processes possibly by downregulating gene expression of angiogenesis factors and proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Objective: To investigate anti-tumor effect of rice bran hydrolysates (RBH) on proliferation, migration, invasion, and angiogenesis of cholangiocarcinoma (CCA) cells, and elucidate the underlying mechanisms. Methods: RBH was prepared from Tubtim Chumprae rice (Oryza sativa L.) by hydrothermolysis followed by protease digestion. Phenolic content in RBH was analyzed by high-performance liquid chromatography. Human CCA cells, KKU-156, KKU-452, and KKU-100, were used to study the effects of RBH on proliferation, migration, invasion, and adhesion by wound healing, Transwell chamber, and fibronectin cell adhesion assays. Angiogenesis was evaluated using human umbilical vein endothelial cells. Proteins associated with cancer progression were analyzed by immunobloting assays. Results: RBH contained carbohydrates, proteins, lipids, and various phenolic compounds and flavonoids. RBH did not inhibit CCA proliferation, but strongly suppressed migration, invasion, adhesion of CCA cells, and the formation of tube-like capillary structures of human umbilical vein endothelial cells. Moreover, RBH down-regulated phosphorylation of FAK, PI3K, and Akt, suppressed NF-κB nuclear translocation, decreased the expression of ICAM-1, vimentin and vascular endothelium growth factor (VEGF), and increased the expression of E-cadherin. Conclusions: RBH suppresses CCA cell migration and invasion and decreases expression of proteins involved in cancer metastasis. RBH is a potential food supplement for cancer prevention. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the immunomodulatory effects of rice bran hydrolysates on cultured immune cells and their underlying mechanism. Methods: Rice bran hydrolysates were prepared from pigmented rice (Oryza sativa L.) by hydrothermolysis and protease digestion. Rice bran hydrolysates were assayed for phenolic content and antioxidant activity. Cell proliferation of Jurkat, THP-1 and peripheral blood mononuclear cells (PBMC) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Chemotaxis was evaluated by transwell chamber methods. Immunoadherence of THP-1 was performed on cultured human umbilical vein endothelial cells (HUVEC). Cytokine released from PBMC was measured by ELISA assay kits. Lymphocyte-mediated cytotoxicity was carried out on KKU-452 cells. Proteins associated with immunomodulation were analyzed by Western immunoblotting assay. Results: Rice bran hydrolysates were rich in phenolic compounds, such as ferulic acid, catechin, quercetin, and quercetin glycosides. Rice bran hydrolysates suppressed phytohemagglutinin (PHA)- stimulated proliferation of PBMC and Jurkat cells, chemotaxis of Jurkat and THP-1 cells, and immunoadherence of THP-1 on HUVEC cultured cells. The cellular mechanism of rice bran hydrolysates involved the activation of AMPK as well as suppression of mTOR, NF-κB and VCAM-1. Rice bran hydrolysates potentiated PBMC on the PHA-stimulated release of IL-2, TNF-α, and IL-4, and enhanced PHA-induced non-MHC-restricted cytotoxicity on KKU-452 cancer cells. Conclusions: The immunomodulatory effect of phytochemicals derived from rice bran hydrolysates suggests its therapeutic potential for further investigation. [ABSTRACT FROM AUTHOR]