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

Kim,Okhwa; Hwangbo,Cheol; Kim,Junhyeong; Li,Dong‑Hao; Min,Byung‑Sun; Lee,Jeong‑Hyung

doi:10.3892/mmr.2015.3621

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

Authors:
- Okhwa Kim
- Cheol Hwangbo
- Junhyeong Kim
- Dong‑Hao Li
- Byung‑Sun Min
- Jeong‑Hyung Lee
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Affiliations: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon‑do 200‑701, 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 712‑702, Republic of Korea
Published online on: April 15, 2015 https://doi.org/10.3892/mmr.2015.3621
Pages: 2161-2168

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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.

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