Song Shei Lin

Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and -9 and Vascular Endothelial Growth Factor (VEGF)

It is well known that matrix metalloproteinases (MMPs) act an important role in the invasion, metastasis and angiogenesis of cancer cells. Agents suppressed the MMPs could inhibited the cancer cells migration and invasion. Numerous evidences had shown that curcumin (the active constituent of the dietary spice turmeric) has potential for the prevention and therapy of cancer. Curcumin can inhibit the formation of tumors in animal models of carcinogenesis and act on a variety of molecular targets involved in cancer development. There is however, no available information to address the effects of curcumin on migration and invasion of human lung cancer cells. The anti-tumor invasion and migration effects of lung cancer cells induced by curcumin were examined. Here, we report that curcumin suppressed the migration and invasion of human non-small cell lung cancer cells (A549) in vitro. Our findings suggest that curcumin has anti-metastatic potential by decreasing invasiveness of cancer cells. Moreover, this action was involved in the MEKK3, p-ERK signaling pathways resulting in inhibition of MMP-2 and -9 in human lung cancer A549 cells. Overall, the above data shows that the anticancer effect of curcumin is also exist for the inhibition of migration and invasion in lung cancer cells.

Diallyl disulfide induces apoptosis in human colon cancer cell line (COLO 205) through the induction of reactive oxygen species, endoplasmic reticulum stress, caspases casade and mitochondrial-dependent pathways

In this study, we investigated the effects of DADS on human colon cancer cell line COLO 205 on cell cycle arrest and apoptosis in vitro. After 24 h treatment of COLO 205 cells with DADS, the dose- and time-dependent decreases of viable cells were observed and the IC50 was 22.47 microM. The decreased percentages of viable cells are associated with the production of ROS. Treatment of COLO 205 cells with DADS resulted in G2/M phase arrest and apoptosis occurrence through the mitochondrial-pathway (Bcl-2, Bcl-xL down-regulation and Bak, Bax up-regulation). DADS increased cyclin B, cdc25c-ser-216-9 and Wee1 but did not affect CDK1 protein and gene expression within 24 h of treatment. DADS-induced apoptosis was examined and confirmed by DAPI staining and DNA fragmentation assay. DADS promoted caspase-3, -8 and -9 activity and induced apoptosis were accompanied by increasing the levels of Fas, phospho-Ask1 and -JNK, p53 and decreasing the mitochondrial membrane potential which then led to release the cytochrome c, cleavage of pro-caspase-9 and -3. The COLO 205 cells were pre-treated with JNK inhibitor before leading to decrease the percentage of apoptosis which was induced by DADS. Inhibition of caspase-3 activation blocked DADS-induced apoptosis on COLO 205 cells.

Amentoflavone inhibits ERK-modulated tumor progression in hepatocellular carcinoma in vitro

BACKGROUND/AIM A previous study indicated that amentoflavone inhibits tumor growth of breast cancer. However, the anti-cancer effects and mechanism of amentoflavone in hepatocellular carcinoma (HCC) have not been elucidated. The aim of the present study was to verify the effect of amentoflavone on tumor progression in HCC. MATERIALS AND METHODS HCC SK-Hep1 cells were treated with different concentrations of amentoflavone or 10 μM PD98059 (extracellular signal-regulated kinases (ERK) inhibitor) for 48 h, respectively, and then cell viability, NF-κB activation, levels of tumor progression-associated proteins, and cell invasion were evaluated with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), NF-κB reporter gene assay, western blotting, and cell invasion assay. RESULTS The results demonstrated that both amentoflavone and PD98059 not only significantly reduced cell viability, NF-κB activation, and cell invasion, but also inhibited the expression of tumor progression-associated proteins. In addition, we found that amentoflavone suppresses ERK phosphorylation. CONCLUSION The results of the present study suggest that amentoflavone down-regulates ERK-modulated tumor progression in HCC.

Amentoflavone Inhibits Hepatocellular Carcinoma Progression Through Blockage of ERK/NF-ĸB Activation

Aim: The aim of the present study was to confirm therapeutic efficacy and find probable mechanism of action of amentoflavone in hepatocellular carcinoma (HCC) in vivo. Materials and Methods: Luciferase reporter vector pGL4.50_transfected SK-Hep1 (SK-Hep1/luc2) tumor-bearing mice were treated with vehicle or amentoflavone (100 mg/kg/day by gavage) for 14 days. Tumor growth, amentoflavone toxicity, and extracellular signal-regulated kinase (ERK)/nuclear factor-kappaB (NF-ĸB) signaling in tumor progression were evaluated with digital caliper, bioluminescence imaging, computed tomography, body weight, pathological examination of liver, and immunohistochemistry staining. Results: Amentoflavone significantly inhibited tumor growth, ERK/NF-ĸB activation, and expression of tumor progression-associated proteins as compared to vehicle-treated group. In addition, body weight and liver morphology of mice were not influenced by amentoflavone treatment. Conclusion: These results suggest that amentoflavone inhibits HCC progression through suppression of ERK/NF-ĸB signaling.

Inhibited Effects of Curcumin on UV-induced Cell Migration and Expression of Matrix Metalloproteinases in Liver Cancer Cells

The aim of this study is to investigate the combined effects of curcumin and ultraviolet (UV) exposure on cell migration and matrix metalloproteinases (MMPs) expression in human liver cancer J5 cells. Human liver cancer J5 cells were cultured with a DMEM medium, and then the cells were treated with and without curcumin. Approximately 18 h later, the medium was removed, and with lids off, the cells were exposed to 150 J/m^2 UV light (312 nm, UV-B) using a UV gene linker apparatus equipped with an energy output control. Cells incubated at 37° in a CO2 incubator for 0, 12, and 24 hours. Finally, the survival rates were assayed by flow cytometry and signal proteins including: MMP-2, MMP-9 and bcl-2 were assayed by western blotting. 25 μM of curcumin decreased the viability by 50% in J5 cells. The viability in cells treated with UV alone decreased slightly in comparison with the control group, and the viability of the combined group was 65% greater than that of the group treated with curcumin alone. UV treatment alone of 150 mJ/cm^2 greatly enhances cell migration and curcumin alone inhibits cell migration. The migration index of the combined group for 12 and 24 hours was 22.5 and 24.5 respectively. The indexes were about 53% and 30% compared with the group treated with UV alone. This study demonstrated that to inhibit cell migration, a combined group treated with UV and curcumin led to decreases of MMP-2 and MMP-9 levels when compared with a group treated with UV alone. The combined group of curcumin and UV induced anti-apoptosis through the bcl-2 expression in J5 cells.

Effects of Ultraviolet B on Cell Motility and Expression of Matrix Metalloproteinase in Liver Cancer Cells

This study aimed to investigate the cell migration and related protein expression including matrix metalloproteinase (MMP-2 & MMP-9), nuclear fator kappa B (NF-KB), and Bcl-2 protein after different doses of ultraviolet exposure in human liver cancer cell (J5 cells). J5 cells (5×10^5) were plated on 100 mm^2 culture dishes, and approximately 18 h later Hams F12K medium was removed, and with lids off, cells were exposed to 50, 100, 150 mJ/cm^2 UV light (312 nm) by using a UV gene linker apparatus equipped with an energy output control. The total proteins were collected at 6 h after UV exposure or cultured for 24 hours. MMP, Bcl-2 and NF-KB were assayed by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Viability of UV treatments was decreased slightly comparing to the control group. Survival rates of the three doses were over 75%. UV treatment of 150 mJ/cm^2 greatly enhanced cell migration with significant difference of statistics and induced over-expression of bcl-2 and MMP-2. However, MMP-9 was not increased after UV exposure. It appeared that low dose UV to increase the relative effects of MMP-2 expression and cell migration. UV exposure increased the expression of NF-KB and Bcl-2 on dose dependent in liver cancer cells. It demonstrated that UVB increased higher expression levels of NF-KB and Bcl-2 than the control group, which promoted the cell migration in liver cancer cells. MMP-2 level increased by the enhanced expression of NF kappa B may be involved with the migration mechanism. Low dose treatment of 150 mJ/cm^2 UVB increased the Bcl-2 expression apparently and showed that low dose UVB irradiation was not sensitive in liver cancer J5 cell.