Abstract. Panax notoginseng (P. notoginseng) and its components are used as traditional Chinese medicine for cardiovascular disease, although studies concerning the anti-metastatic properties of these compounds are limited. The goal of this study was to investigate the effects of notoginsenoside R1 (NGR1), an important compound derived from P. notoginseng, on the metastasis of human colorectal cancer (CRC). The migratory, invasive, and adhesive abilities of cultured human CRC cells (HCT-116) treated with NGR1 and expression of metastasis-associated regulatory molecules were assessed. The migratory and invasive abilities of the HCT-116 cells were reduced after treatment with 75, 150 or 300 µM NGR1 for 24 h. When HCT-116 cells were incubated with 150 or 300 µM NGR1 for 24 h, matrix metalloproteinase (MMP)-9 expression was reduced compared with that of the control group. In the adhesion reaction assays, treatment with 150 or 300 µM NGR1 led to significantly decreased adhesion of the HCT-116 cells to endothelial cells (EA.hy926 cells). Levels of integrin-1 protein were significantly decreased in the HCT-116 cells following treatment with 75, 150 or 300 µM NGR1, and levels of E-selectin and intercellular adhesion molecule 1 (ICAM-1) proteins were significantly decreased in the EA.hy926 cells treated with 75, 150 or 300 µM NGR1. Scanning electron microscopy examination indicated that HCT-116 cells treated with lipopolysaccharide (LPS) combined with 300 µM NGR1 exhibited a less flattened and retracted shape compared with cells treated with LPS alone, and this change in shape is characteristic of extravasation. Additionally, the transepithelial electrical resistance of the EA.hy926 endothelial cell monolayer increased after incubation with 150 or 300 µM NGR1 for 24 h. Overall, these results demonstrated the anti-metastatic properties of 150 or 300 µM NGR1, a compound that affects CRC metastasis by inhibiting cell migration, invasion, and adhesion and by regulating expression of metastasis-associated signalling molecules.

The goal of this study was to investigate the effect of the Panax notoginseng ethanol extract (PNEE) on the regulation of human colorectal cancer (CRC) metastasis. The migratory, invasive, and adhesive abilities and the expression of metastasis-associated regulatory molecules in cultured human CRC cells (HCT-116) treated with the PNEE were analyzed in this study. The migratory and invasive abilities of HCT-116 cells were reduced after PNEE treatment. The incubation of HCT-116 cells with the PNEE for 24 h decreased MMP-9 expression and increased E-cadherin expression compared with the control group. The adhesion reaction assay indicated that treatment with the PNEE led to significantly decreased HCT-116 adhesion to endothelial cells (EA.hy926 cells). The integrin-1 protein levels in HCT-116 cells were significantly decreased following treatment with the PNEE. Similarly, the protein levels of E-selectin and intercellular adhesion molecule-1 (ICAM-1) were significantly decreased by treatment of the EA.hy926 endothelial cells with PNEE. A scanning electron microscope (SEM) examination indicated that HCT-116 cells treated with LPS combined with the PNEE had a less flattened and retracted shape compared with LPS-treated cells, and this change in shape was found to be a phenomenon of extravasation invasion. The transepithelial electrical resistance (TEER) of the EA.hy926 endothelial cell monolayer increased after incubation with the PNEE for 24 h. A cell-cell permeability assay indicated that HCT-116 cells treated with the PNEE displayed significantly reduced levels of phosphorylated VE-cadherin (p-VE-cadherin). These results demonstrate the antimetastatic properties of the PNEE and show that the PNEE affects cells by inhibiting cell migration, invasion, and adhesion and regulating the expression of metastasis-associated signaling molecules.

Abstract. Sedanolide (SN), a phthalide-like compound from celery seed oil, possesses antioxidant effects. However, the effect of SN on cell death in human liver cancer cells has yet to be determined. In this study, cell viability determination, monodansylcadaverine (MDC) fluorescent staining and immunoblot analysis were performed to determine autophagy induction and autophagy-induced protein expression changes via molecular examination after human liver cancer (J5) cells were treated with SN. Our studies demonstrate that SN suppressed J5 cell viability by inducing autophagy. Phosphoinositide 3-kinase (PI3K)-I, mammalian target of rapamycin (mTOR) and Akt protein levels decreased, whereas PI3K-III, LC3-II and Beclin-1 protein levels increased following SN treatment in J5 cells. In addition, SN treatment upregulated nuclear p53 and damage-regulated autophagy modulator (DRAM) and downregulated cytosolic p53 and Tp53-induced glycolysis and apoptosis regulator (TIGAR) expression in J5 cells. Furthermore, the cytosolic phosphorylation of inhibitor of kappa B (IκB) and nuclear p65 and the DNA-binding activity of NF-κB increased after SN treatment.These results suggest that SN induces J5 cell autophagy by regulating PI3K, p53 and NF-κB autophagy-associated signaling pathways in J5 cells. IntroductionHuman hepatocellular carcinoma (HCC) is one of the most common malignant tumors and a significant cause of mortality in several regions of Africa and Asia (1,2). Triggering cancer cell death to reduce cancer cell number and inhibiting cancer cell proliferation by phytochemicals or chemotherapeutic agents represent some of the most effective current anticancer strategies (3). Cell death can occur through one of three pathways: necrosis, apoptosis or autophagy (4).Autophagy is induced by various physiological conditions, such as mitochondrial damage, protein aggregation, pathogen infection and nutrient starvation (5,6). Autophagy is a multi-step cellular pathophysiological program, including initiation (pre-autophagosome formation), autophagosome formation, maturation and degradation (7). In these steps, phosphoinositide 3-kinases (PI3Ks) play key regulatory roles in many cellular processes, including cell survival, proliferation and differentiation (8-10). Both class I PI3K (PI3K-I)/Akt/ mammalian target of rapamycin (mTOR) and Beclin-1/class III PI3K (PI3K-III)/LC3-II signaling pathways are involved in pre-autophagosome formation (11-14). Cytosolic and nuclear p53, damage-regulated autophagy modulator (DRAM) and the p53-induced glycolysis and apoptosis regulator (TIGAR) are involved in autophagosome formation (15). In addition, p53 initiates a cascade of starvation signals and triggers a starvation-like response by inhibiting mTOR (16). Furthermore, p53 activates both the DRAM and PI3K-III pathways upon autophagosome formation (15). Phytochemicals or chemical agents that regulate p53-and PI3K-mediated autophagy induction could serve as a potential starting point for novel methods of cancer prevention and treatment.The transc...

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