Byeong-Soo Kim

Apoptotic Effect of Quercetin on HT-29 Colon Cancer Cells via the AMPK Signaling Pathway

Activation of AMP-activated protein kinase (AMPK), a physiological cellular energy sensor, strongly suppresses cell proliferation in both nonmalignant and tumor cells. This study demonstrates the mechanism of quercetin-induced apoptosis in HT-29 colon cancer cells. Treatment of cells with quercetin significantly decreased cell viability in a dose-dependent manner. Notably, quercetin increased cell cycle arrest in the G1 phase and up-regulated apoptosis-related proteins, such as AMPK, p53, and p21, within 48 h. Furthermore, in vivo experiments showed that quercetin treatment resulted in a significant reduction in tumor volume over 6 weeks, and apoptosis-related protein induction by quercetin was significantly higher in the 100 mg/kg treated group compared to the control group. All of these results indicate that quercetin induces apoptosis via AMPK activation and p53-dependent apoptotic cell death in HT-29 colon cancer cells and that it may be a potential chemopreventive or therapeutic agent against HT-29 colon cancer.

Curcumin suppresses the TPA-induced invasion through inhibition of PKCα-dependent MMP-expression in MCF-7 human breast cancer cells.

Curcumin (diferuloylmethane) is a polyphenol derived from the plant turmeric (Curcuma longa), which is commonly used as a spice. Although anti-carcinogenic, anti-oxidant, anti-inflammation, and anti-angiogenic properties have been reported, the effect of curcumin on breast cancer metastasis is unknown. Matrix metalloproteinase-9 (MMP-9) is a major component in cancer cell invasion. In this study, we investigated the inhibitory effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion and the molecular mechanisms involved in MCF-7 cells. Our results showed that curcumin inhibits TPA-induced MMP-9 expression and cell invasion through suppressing NF-κB and AP-1 activation. Also, curcumin strongly repressed the TPA-induced phosphorylation of p38 and JNK and inhibited TPA-induced translocation of PKCα from the cytosol to the membrane, but did not affect the translocation of PKCδ. These results indicate that curcumin-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the PKCα, MAPK and NF-κB/AP-1 pathway in MCF-7 cells. Curcumin may have potential value in restricting breast cancer metastasis.

Sulforaphane controls TPA-induced MMP-9 expression through the NF-κB signaling pathway, but not AP-1, in MCF-7 breast cancer cells.

Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane] is an isothiocyanate found in some cruciferous vegetables, especially broccoli. Sulforaphane has been shown to display anti-cancer properties against various cancer cell lines. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in cancer cell invasion. In this study, we investigated the effect of sulforaphane on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. TPA-induced MMP-9 expression and cell invasion were decreased by sulforaphane treatment. TPA substantially increased NF-κB and AP-1 DNA binding activity. Pre-treatment with sulforaphane inhibited TPA-stimulated NF-κB binding activity, but not AP-1 binding activity. In addition, we found that sulforaphane suppressed NF-κB activation, by inhibiting phosphorylation of IκB in TPA-treated MCF-7 cells. In this study, we demonstrated that the inhibition of TPA-induced MMP-9 expression and cell invasion by sulforaphane was mediated by the suppression of the NF-κB pathway in MCF-7 cells. [BMB Reports 2013; 46(4): 201-206]

Brazilin inhibits UVB-induced MMP-1/3 expressions and secretions by suppressing the NF-κB pathway in human dermal fibroblasts.

Brazilin (7, 11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10 (6H)-tetrol), the major component of Caesalpinia sappan L., is a natural red pigment used for histological staining. Recent studies have shown that brazilin exhibits distinct biological effects, including anti-hepatotoxicity, antiplatelet activity, and anti-inflammatory activities. In the present study, we evaluated the effects of brazilin on MMP-1 and -3 expressions in human dermal fibroblasts exposed to ultraviolet B (UVB) irradiation. Brazilin showed protective effect on UVB-induced loss of cell viability of fibroblasts. Brazilin also blocked significantly UVB-induced Reactive Oxygen Species generation in fibroblasts. Brazilin inhibited UVB-induced MMP-1/3 expressions and secretions in a dose-dependent manner. Moreover, UVB-induced NF-κB activation was completely blocked by treatment with brazilin. These findings suggest that brazilin inhibits UVB-induced MMP-1/3 expressions and secretions by suppressing of NF-κB activation in human dermal fibroblasts. Thus, brazilin might be used as a potential agent for treatment of UV-induced skin photoaging.

Peroxisome Proliferator-Activated Receptor γ and Retinoic Acid Receptor Synergistically Up-Regulate the Tumor Suppressor PTEN in Human Promyeloid Leukemia Cells

Peroxisome proliferator-activated receptor γ (PPARγ) and retinoic acid receptors (RARs) have been a focus in chemotherapy for human cancers. The tumor suppressor PTEN plays a pivotal role in the growth of human cancer cells. We investigated whether costimulation of PPARγ and RAR could synergistically up-regulate PTEN in human leukemia cells and consequently potentiate the inhibition of growth and cell cycle progression of these cells. We found that overexpression of PTEN with the adenoviral vector Ad/PTEN caused growth arrest at the G1 phase of the cell cycle of HL-60 cells. HL-60 cells treated with either a PPARγ ligand (ciglitazone) or a RAR ligand(all-trans retinoic acid [ATRA]) up-regulated PTEN in HL-60 cells. The 2 compounds in combination showed synergistic effects on PTEN expression at the protein and messenger RNA levels. Moreover, the combination of ciglitazone and ATRA synergistically reduced cell growth rates and cell cycle arrest at the G1 phase. Our results suggest that, PPARγ and RAR play an important role in controlling the growth of leukemia cells via the up-regulation of PTEN.

Dihydroavenanthramide D inhibits human breast cancer cell invasion through suppression of MMP-9 expression.

Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Previous study demonstrates that DHAvD strongly inhibits activation of nuclear factor-kappa B (NF-κB), which is a major component in cancer cell invasion. The present study investigated whether DHAvD can modulate MMP-9 expression and cell invasion in MCF-7 human breast cancer cells. MMP-9 expression and cell invasion in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) was increased, whereas these inductions were muted by DHAvD. DHAvD also suppressed activation of mitogen-activated protein kinase (MAPK), and MAPK-mediated nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activations in TPA-treated MCF-7 cells. The results indicate that DHAvD-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the MAPK/NF-κB and MAPK/AP-1 pathways in MCF-7 cells. DHAvD may have potential value in breast cancer metastasis.

Tumor necrosis factor-α enhances DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK pathway

The differentiation of promyelocytic leukemic cells into mature cells is the major strategy for drug-based treatment of leukemia. Higher efficient methods to differentiate promyelocytic leukemic cells have been developed using various differentiation inducers including interferon-α, interleukin-4, tumor necrosis factor-α (TNF-α), and dimethyl sulfoxide (DMSO) as a single agent or in combination with each other. Here, we show that a combination of TNF-α with DMSO shows a synergic effect on HL-60 cell differentiation through the activation of ERK pathway. TNF-α enhanced CD11b expression and percent of cell population in the G1 phase induced by DMSO, which are hallmarks for HL-60 cell differentiation. Inhibition of ERK pathway abolished the synergic effect of TNF-α in combination with DMSO on HL-60 differentiation, but the inhibition NF-κB pathway did not. These results suggest that TNF-α synergistically increases DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK-signaling pathway.

Membrane cholesterol is required for activity of Vibrio vulnificus cytolysin

Vibrio vulnificus cytolysin (VVC) forms a pore in the plasma membrane and induces cytolysis of various cells including erythrocytes, neutrophil and endothelial cells. The cytolytic activity of VVC is inhibited by exogenously added cholesterol, suggesting that membrane cholesterol might be required for VVC cytolytic activity. However, there is no direct evidence that membrane cholesterol is involved in VVC-induced cytolysis. Herein we demonstrate that membrane cholesterol is required for binding of VVC to the plasma membrane. Membrane cholesterol depletion with methyl-β-cyclodextrin inhibited VVC-induced K+ release, 2-deoxy glucose release and Ca2+ influx, which are indicators of VVC pore formation. The cholesterol depletion-induced blockage of VVC cytolysis was due to the inhibition of VVC binding to membrane. These findings suggest that interaction with cholesterol is required for activity of VVC.

Use of a phase type elongated circular grating in Talbot moiré deflectometry

Summary We analyze theoretically and experimentally the self-image of a phase type elongated circular (EC) grating which has a periodic structure of rectangular type, so that it can be employed in Talbot moire deflectometry. We examine the visibility of a self-imaged phase EC grating while the optical phase difference of the grating is varied. We show that the self-image of a phase EC grating of rectangular type is slightly aberrated around the center of the interface of linear and semicircular parts but moire fringes by self-imaging a phase EC grating on a reference EC grating are little influenced by the image aberration. We conclude that a phase EC grating as well as an amplitude EC grating in our earlier work [Optik 113 (2002) 285] can be effectively applied to a Talbot interferometer when the phase difference of the grating is prepared close to 90°.

Vibrio vulnificus cytolysin induces hyperadhesiveness of pulmonary endothelial cells for neutrophils through endothelial P-selectin: a mechanism for pulmonary damage by Vibrio vulnificus cytolysin.

Vibrio vulnificus cytolysin forms transmembrane pores that are permeable to calcium ions in pulmonary endothelial cells, and has been suggested as an important virulence factor that sequestrate neutrophils primarily in the lung. To elucidate the mechanism we investigated whether the cytolysin affect the expression of endothelial P-selectin and adhesiveness of pulmonary endothelial cells for neutrophils. The cytolysin increased the adhesiveness of CPAE cell, a pulmonary endothelial cell line, for neutrophils in a concentrationand time-dependent manner. The increase of adhesiveness occurred within several minutes after the cytolysin exposure, persisted up to 90 min, and was not affected by cycloheximide. Furthermore, flow cytometric analyses showed that cytolysin enhanced the level of P-selectin on CPAE cell surface. Therefore, these results suggest that the cytolysin-induced hyperadhesiveness of pulmonary endothelial cells for neutrophils is mediated by the mobilization of endothelial P-selectin to the cell surface.