Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8323351 | The International Journal of Biochemistry & Cell Biology | 2014 | 9 Pages |
Abstract
2â²-Hydroxycinnamaldehyde inhibits breast cancer cell invasion. This study examined whether 2â²-hydroxycinnamaldehyde, acting as a Michael acceptor, interferes with the ligand binding of low-density lipoprotein receptor-related protein 1 to mediate breast cancer cell invasion. Low-density lipoprotein receptor-related protein 1, one of the direct molecular targets of 2â²-hydroxycinnamaldehyde, is a multifunctional endocytic receptor. Changes in the thiol oxidation status of cell surface receptor proteins may function as a molecular switch, influencing ligand(s) binding. The oxidation status of extracellular cysteine thiol groups in MCF-7 and MDA-MB-231 cells was examined using a fluorescence-activated cell sorter with thiol-specific fluorescent probes; Matrigel invasion and wound-healing assays were performed to determine the effects of 2â²-hydroxycinnamaldehyde on in vitro cell migration. The molecular mechanisms by which 2â²-hydroxycinnamaldehyde acts were evaluated by transient knockdown using siRNA or inhibition of low-density lipoprotein receptor-related protein 1 by receptor-associated protein treatment. 2â²-Hydroxycinnamaldehyde increased α-2-macroglobulin binding to low-density lipoprotein receptor-related protein 1, which was alleviated by pretreatment of cells with N-acetylcystein. 2â²-Hydroxycinnamaldehyde decreased the extracellular pepsin concentration significantly in a low-density lipoprotein receptor-related protein 1- and α-2-macroglobulin-dependent manner. The anti-invasive effect of 2â²-hydroxycinnamaldehyde was mitigated with receptor-associated protein pretreatment, suggesting that low-density lipoprotein receptor-related protein 1 is essential for the effects of 2â²-hydroxycinnamaldehyde. From these data, we suggest that 2â²-hydroxycinnamaldehyde increases the cysteine thiol oxidation status of low-density lipoprotein receptor-related protein 1 extracellular domains, which results in α-2-macroglobulin ligand binding stimulation. Therefore, pepsin clearance in a low-density lipoprotein receptor-related protein 1-α-2-macroglobulin-dependent manner might be an important molecular mechanism in 2â²-hydroxycinnamaldehyde exerting its anti-invasive action on breast cancer cells. Furthermore, our data may provide an opportunity to promote the importance of the thiol oxidation status of cell surface receptor proteins for regulating cellular signaling pathways that are important in cancer progression.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Hye Suk Kang, JinKyoung Kim, Heon-Jin Lee, Byoung-Mog Kwon, Dong-Ki Lee, Su-Hyung Hong,