title: Inhibition of human colorectal cancer metastasis by notoginsenoside R1, an important compound from Panax notoginseng.
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.
authors.affiliation: Department of Chinese Medicine, E-DA Hospital, Kaohsiung 84001, Taiwan, R.O.C.
authors.forename: Chang-Yin
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung 81157, Taiwan, R.O.C.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Hsieh
authors.affiliation: Department of Chemistry, National Sun Yat-sen University, Kaohsiung 80424, Taiwan, R.O.C.
authors.forename: Shuchen
authors.initials: S
authors.lastname: Hsieh
authors.affiliation: Department of Chinese Medicine, E-DA Hospital, Kaohsiung 84001, Taiwan, R.O.C.
authors.forename: Chin-Chung
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Department of Dietetics, Kaohsiung Municipal United Hospital, Kaohsiung 80457, Taiwan, R.O.C.
authors.forename: Lan-Chi
authors.initials: LC
authors.lastname: Hsieh
authors.affiliation: Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung 81157, Taiwan, R.O.C.
authors.forename: Yu-Hao
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Department of Nutrition and Health Sciences, Chang Jung Christian University, Tainan 71101, Taiwan, R.O.C.
authors.forename: Chih-Chung
authors.initials: CC
authors.lastname: Wu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D045325:HCT116 Cells / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053723:Panax notoginseng / Q000737:chemistry; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019040:E-Selectin; D036145:Ginsenosides; C546936:SELE protein, human; D018799:Intercellular Adhesion Molecule-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C072936:notoginsenoside R1