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Chelidonine suppresses migration and invasion of MDA-MB-231 cells by inhibiting formation of the integrin-linked kinase/PINCH/α-parvin complex

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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.
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Document Type: Research Article

Affiliations: 1: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwondo 200701, Republic of Korea 2: Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Yanbian University, Yanji, Jilin 133002, P.R. China 3: College of Pharmacy, Catholic University of Daegu, Gyeongsan, North Gyeongsang 712702, Republic of Korea

Publication date: August 1, 2015

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  • 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.
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