Demethoxycurcumin suppresses migration and invasion of MDA-MB-231 human breast cancer cell line.
Demethoxycurcumin (DMC) is one of the main active compounds of curcuminoids found in turmeric powder, which is used as a spice in Asian cooking and traditional medicine. Recent studies reveal that DMC has several biological activities including anti-inflammation and anti-cancer activities. However, the molecular mechanism by which DMC has anti-metastasis activity in breast cancer cells remains poorly understood. Here, we report for the first time that DMC inhibited adhesion, migration and invasion of MDA-MB-231 human breast cancer cells. For cancer cell migration and invasion, extracellular matrix (ECM) degradation processes are required. MDA-MB-231 cells treated with DMC had decreased levels of ECM degradation-associated proteins including matrix metalloproteinase-9 (MMP-9), membrane type-1 matrix metalloproteinase (MT1-MMP), urokinase plasminogen activator (uPA) and uPA receptor (uPAR), while the level of uPA inhibitor (PAI-1) was up-regulated. Moreover, DMC also reduced the expression of intercellular adhesion molecule-1 (ICAM-1) and chemokine receptor 4, (CXCR4), which is involved in modulation of the tumor metastasis process. We also found that DMC treatment inhibited the DNA binding activity of nuclear factor-kappa B (NF-kappaB), which is known to mediate the expression of MMPs, uPA, uPAR, ICAM-1, and CXCR4. These findings strongly suggest that the mechanism of DMC-mediated anti-invasive activity involves modulation of the expression of invasion-associated proteins, possibly by targeting NF-kappaB in MDA-MB-231 cells.
Yodkeeree
Supachai
S
Deparment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Ampasavate
Chadarat
C
Sung
Bokyung
B
Aggarwal
Bharat B
BB
Limtrakul
Pornngarm
P
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D036381:Diarylheptanoids; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis; D019718:Receptors, CXCR4 / Q000378:metabolism
C527276:CXCR4 protein, human; D036381:Diarylheptanoids; D016328:NF-kappa B; D019718:Receptors, CXCR4; D018799:Intercellular Adhesion Molecule-1; D004247:DNA; D003474:Curcumin; C050229:demethoxycurcumin