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

Abstract

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 anti-migratory and anti-invasive effects of chelidonine remain unknown. The aim of the present study was to investigate the inhibitory effects of chelidonine on migration and invasion of MDA-MB-231 human breast cancer cells, and to determine the underlying mechanisms. Chelidonine was shown to inhibit the migration and invasion of MDA-MB-231 cells in a concentration-dependent manner, without affecting the cell viability. Chelidonine did not significantly inhibit the adhesion of the cells to type 1 collagen (COL-I), however it did affect cell spreading and reorganization of the actin cytoskeleton. Chelidonine also inhibited COL-I-induced 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 COL-I-induced formation of the IPP complex and activation of IPP downstream signaling molecules, such as extracellular signal-regulated kinase (ERK)1/2. These results suggest that chelidonine exhibits anti-migratory and anti-invasive effects in MDA-MB-231 cells, by suppressing COL-I-induced integrin signaling, through inhibiting the formation of the IPP complex and subsequent down-regulation 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.

• Authors: Okhwa Kim, Cheol Hwangbo, Junhyeong Kim, Dong-Hao Li, Byung-Sun Min, Jeong-Hyung Lee
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 2 Pg. 2161-8 (Aug 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25890994 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Anticarcinogenic Agents
• Antineoplastic Agents, Phytogenic
• Benzophenanthridines
• LIM Domain Proteins
• LIMS1 protein, human
• Membrane Proteins
• Microfilament Proteins
• PARVA protein, human
• chelidonine
• integrin-linked kinase
• Protein Serine-Threonine Kinases

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Anticarcinogenic Agents (pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Benzophenanthridines (pharmacology)
• Breast (drug effects, metabolism, pathology)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Female
• Humans
• LIM Domain Proteins (metabolism)
• Membrane Proteins (metabolism)
• Microfilament Proteins (metabolism)
• Neoplasm Invasiveness (pathology, prevention & control)
• Protein Serine-Threonine Kinases (metabolism)