Metastasis is the primary cause of cancer-associated mortality. The ternary IPP complex of integrin-linked kinase, PINCH and parvin functions as a signaling platform for integrins, which modulate numerous cellular processes including cell migration and invasion. Chelidonine, isolated
from Chelidonium majus, is a benzophenanthridine alkaloid that exhibits anticancer properties; however, the antimigratory and antiinvasive effects of chelidonine remain unknown. The aim of the present study was to investigate the inhibitory effects of chelidonine on migration and invasion
of MDAMB231 human breast cancer cells, and to determine the underlying mechanisms. Chelidonine was shown to inhibit the migration and invasion of MDAMB231 cells in a concentrationdependent manner, without affecting the cell viability. Chelidonine did not significantly inhibit the adhesion
of the cells to type 1 collagen (COLI), however it did affect cell spreading and reorganization of the actin cytoskeleton. Chelidonine also inhibited COLIinduced protein kinase B (Akt) activation and translocation to the plasma membrane, however, it did not significantly inhibit the activation
of focal adhesion kinase. Notably, chelidonine treatment significantly inhibited COLIinduced formation of the IPP complex and activation of IPP downstream signaling molecules, such as extracellular signalregulated kinase (ERK)1/2. These results suggest that chelidonine exhibits antimigratory
and antiinvasive effects in MDAMB231 cells, by suppressing COLIinduced integrin signaling, through inhibiting the formation of the IPP complex and subsequent downregulation of IPP downstream signaling molecules, such as Akt and ERK1/2. These results suggest that chelidonine may be a potential
therapeutic agent against metastasis of invasive human cancer cells.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
Document Type: Research Article
Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwondo 200701, Republic of Korea
Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Yanbian University, Yanji, Jilin 133002, P.R. China
College of Pharmacy, Catholic University of Daegu, Gyeongsan, North Gyeongsang 712702, Republic of Korea
Publication date: August 1, 2015
More about this publication?
Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
- Editorial Board
- Information for Authors
- Submit a Paper
- Subscribe to this Title
- Information for Advertisers
- Terms & Conditions
- Ingenta Connect is not responsible for the content or availability of external websites