Our findings suggest that resveratrol exerts anti-nephrolithic potential via inhibition of ROS, MCP-1 hyaluronan and OPN signaling.

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The metabolic syndrome creates risk factors for coronary heart disease, diabetes, fatty liver, obesity and several cancers. Our group has already reported that the essential oil from leaves of Pinus koraiensis SIEB (EOPK) exerted antihyperlipidemic effects by upregulating the low-density lipoprotein receptor and inhibiting acyl-coenzyme A, cholesterol acyltransferases. We evaluated in the current study the anti-diabetic effects of EOPK on mice with streptozotocin (STZ)-induced type I diabetes and on HIT-T15 pancreatic β cells. EOPK significantly protected HIT-T15 cells from STZ-induced cytotoxicity and reduced the blood glucose level in STZ-induced diabetic mice when compared with the untreated control. EOPK consistently and significantly suppressed the α-amylase activity in a dose-dependent manner and enhanced the expression of insulin at the mRNA level in STZ-treated HIT-T15 cells, while the expression of insulin was attenuated. EOPK also significantly abrogated the population of reactive oxygen species when compared to the untreated control in STZ-treated HIT-T15 cells. Furthermore, EOPK significantly reduce nitric oxide production, suppressed the phosphorylation of endothelial nitric oxide (NO) synthase and suppressed the production of vascular endothelial growth factor (VEGF) in STZ-treated HIT-T15 cells, implying its potential application to diabetic retinopathy. Overall, our findings suggest that EOPK had hypoglycemic potential by inhibiting reactive oxygene species (ROS), endothelial NO synthase (eNOS) and VEGF in STZ-treated mice and HIT-T15 pancreatic β cells as a potent anti-diabetic agent.

Cluster of differentiation (CD) 44 and epidermal growth factor (EGF) are closely involved in cellular migration and have been used as stem cell markers. Although the hyaluronan (HA)-binding CD44 is responsible for enhanced cellular motility, the mechanism underlying its actions in various cell types and clinical conditions have yet to be elucidated. In the present study, the multikinase inhibitor sorafenib was used to investigate the diverse effects of EGF stimulation on epithelial-mesenchymal transition (EMT) in ovarian cancer cells using immunoblotting and reverse transcription-polymerase chain reaction. In addition, the association between EGF and CD44/HA signaling pathways in the control of mesenchymal phenotype was determined by gene silencing with small interfering RNA transfection. EGF stimulation of ovarian cancer cells increased cellular migration, mesenchymal transition, CD44 expression and the activation of matrix metalloproteinase (MMP)-2 and MMP-9. Sorafenib effectively suppressed the loss of epithelial characteristics in EGF-treated SK-OV-3 ovarian cancer cells, via targeting the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. Although treatment of Caov-3 ovarian cancer cells with sorafenib blocked the expression of mesenchymal phenotypes following EGF stimulation, EGF-activated Caov-3 cells exhibited reduced MAPK/ERK signaling. Furthermore, EGF-activated Caov-3 cells increased the expression of hyaluronan synthase 2 and HA-CD44 ligation in EGF-exposed Caov-3 cells, which resulted in the activation of the Ras/Raf/MEK signaling pathway, amplification of migratory activity and the expression of mesenchymal markers, including N-cadherin and vimentin. Furthermore, silencing EGFR in SK-OV-3 cells and CD44 in Caov-3 cells suppressed their migratory activity, through inhibition of the MAPK/ERK pathway. The present results suggested that EGF-mediated signaling may regulate metastasis and invasion of ovarian cancer cells, in a cancer cell type-dependent manner.

The underlying antimetastatic mechanism of anethole (1) still remains unclear in association with the molecules of the epithelial to mesenchymal transition (EMT). Herein, the role of the EMT molecules was elucidated in terms of the antimetastatic activity of 1 using DU145 cells. Anethole significantly inhibited the adhesion of DU145 cells to vitronectin-coated plates, as well as migration in a wound-healing assay and invasion using a Boyden chamber. Also, anethole suppressed the expression of MMP-9 in DU145 cells by zymography, ELISA, and RT-PCR. Consistently, the silencing of MMP-9 enhanced the activity of 1 to upregulate the expression of E-cadherin and to attenuate the expression of Vimentin in DU145 cells. Compound 1 enhanced E-cadherin, which is an epithelial marker and attenuated the expression of Vimentin, Twist, and Snail as mesenchymal molecules at the mRNA level. Consistently, anethole upregulated E-cadherin and downregulated the expression of Vimentin, Twist and PI3K, and AKT at the protein level in DU145 cells. Conversely, the antimetastatic effects of 1 to inhibit invasion and the expression of MMP-9 and upregulate E-cadherin were reversed by the EMT inducer TGF-β in DU145 cells. Overall, the present findings suggest that anethole exerts antimetastatic activity via regulation of crosstalk between EMT molecules and MMP-9 on the basis of the in vitro data obtained.