demethoxycurcumin and Neoplasm-Metastasis

Demethoxycurcumin (DMC), one of the curcuminoids present in turmeric, has been shown to induce cell death in many human cancer cell lines, however, there has not been any investigation on whether DMC inhibits metastatic activity in human cervical cancer cells in vitro. In the present study, DMC at 2.5-15 μM decreased cell number, thus, we used IC. The wound healing, migration, invasion, zymography, and western blotting assays were used to investigate the effects of DMC on HeLa cells.. The wound healing assay was used to show that DMC suppressed cell movement of HeLa cells. Furthermore, the trans-well chamber assay was used to show that DMC suppressed HeLa cell migration and invasion. Gelatin zymography assay did not show any significant effects of DMC on the gelatinolytic activity (MMP-2 and -9) in conditioned media of HeLa cells treated by DMC. Western blotting showed that DMC significantly reduced protein levels of GRB2, MMP-2, ERK1/2, N-cadherin and Ras but increased the levels of E-cadherin and NF-κB in HeLa cells. Confocal laser microscopy indicated that DMC increased NF-κB in HeLa cells confirming the results from Western blotting.. DMC may be used as a novel anti-metastatic agent for the treatment of human cervical cancer in the future.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Movement; Culture Media, Conditioned; Curcumin; Diarylheptanoids; Drug Screening Assays, Antitumor; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Matrix Metalloproteinases; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; NF-kappa B

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.

Topics: Animals; Breast Neoplasms; Cell Adhesion; Cell Line, Tumor; Cell Movement; Curcumin; Diarylheptanoids; DNA; Extracellular Matrix; Gene Expression Regulation, Neoplastic; Humans; Intercellular Adhesion Molecule-1; Neoplasm Invasiveness; Neoplasm Metastasis; NF-kappa B; Receptors, CXCR4