Anti-invasive activity of sanguinarine through modulation of tight junctions and matrix metalloproteinase activities in MDA-MB-231 human breast carcinoma cells.
Tight junctions (TJs) are critical structures for the maintenance of cellular polarity, acting as paracellular permeability barriers and playing an essential role in regulation of the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. Matrix metalloproteinases (MMPs) have been implicated as possible mediators of invasiveness and metastasis in some cancers. In this study, it was investigated the effect of sanguinarine, a benzophenanthridine alkaloid, on the correlation between the tightening of TJs and the anti-invasive activity in human breast carcinoma MDA-MB-231 cells. The inhibitory effects of sanguinarine on cell proliferation, motility and invasiveness were found to be associated with the increased tightness of the TJ, which was demonstrated by an increase in transepithelial electrical resistance (TER). Additionally, immunoblotting results indicated that sanguinarine repressed the levels of the claudin proteins, major components of TJs that play a key role in the control and selectivity of paracellular transport. Furthermore, the activities of MMP-2 and -9 in MDA-MB-231 cells were dose-dependently inhibited by treatment with sanguinarine, and this was also correlated with a decrease in the expression of their mRNA and proteins.
Choi
Yung Hyun
YH
Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, South Korea. choiyh@deu.ac.kr
Choi
Woo Young
WY
Hong
Su Hyun
SH
Kim
Sung Ok
SO
Kim
Gi-Young
GY
Lee
Won Ho
WH
Yoo
Young Hyun
YH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D053119:Benzophenanthridines / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D017097:Electric Impedance; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D007546:Isoquinolines; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; C005705:sanguinarine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9