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ABSTRACT: Curcumin (diferuloylmethane) is a polyphenol derived from turmeric (Curcuma longa), which is commonly used as a spice. Recent studies have shown that curcumin has a wide range of pharmacological activities, including anticarcinogenic, antioxidant, anti-inflammatory and antiangiogenic activities. However, the antiphotoageing effects of curcumin have yet to be characterized. In this study, we investigated the inhibitory effects of curcumin on matrix metalloproteinase (MMP)-1 and MMP-3 expression in human dermal fibroblast cells. Western blot analysis revealed that curcumin inhibited ultraviolet (UV) B-induced MMP-1 and MMP-3 expression. Furthermore, curcumin significantly blocked UVB-induced reactive oxygen species generation in fibroblasts. Curcumin treatment significantly blocked the UVB-induced activation of nuclear factor (NF)-κB and activator protein (AP)-1. Additionally, curcumin strongly repressed the UVB-induced phosphorylation of p38 and c-Jun N-terminal kinase. Curcumin prevented UVB-induced MMP expression through mitogen-activated protein kinase/NF-κB inhibition and AP-1 activation. In conclusion, curcumin may be useful for preventing and treating skin photoageing.
Experimental Dermatology 05/2013; 22(5):371-4. · 3.54 Impact Factor
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Young-Rae Lee,
Eun-Mi Noh,
Ji-Hey Han,
Jeong-Mi Kim,
Bo-Mi Hwang,
Byeong-Soo Kim,
Sung-Ho Lee,
Sung Hoo Jung,
Hyun Jo Youn,
Eun Yong Chung, Jong-Suk Kim
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ABSTRACT: 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].
BMB reports 04/2013; 46(4):201-6. · 1.72 Impact Factor
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Jeong-Mi Kim,
Eun-Mi Noh,
Kang-Beom Kwon, Jong-Suk Kim,
Yong-Ouk You,
Jin-Ki Hwang,
Bo-Mi Hwang,
Min-Suk Kim,
Seung-Jin Lee,
Sung-Hoo Jung,
Hyun-Jo Youn,
Eun-Yong Chung,
Young-Rae Lee
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ABSTRACT: Cell invasion is required for neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in the process of cancer cell invasion. Sulfuretin is one of the major flavonoids isolated from Rhus verniciflua. Sulfuretin has been used to reduce oxidative stress, platelet aggregation, the inflammatory response and mutagenesis. However, the effect of sulfuretin on breast cancer metastasis is unknown. In this study, we investigated the inhibitory effect of sulfuretin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. Sulfuretin inhibited TPA-induced transcriptional activation of nuclear factor-κB (NF-κB). We demonstrated that sulfuretin mediated the inhibition of TPA-induced MMP-9 expression and that cell invasion in MCF-7 cells involved suppression of the NF-κB pathway. Therefore, inhibiting MMP-9 expression by sulfuretin may have therapeutic potential for controlling breast cancer invasiveness.
Oncology Reports 12/2012; · 1.84 Impact Factor
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ABSTRACT: Νuclear factor-κB (NF-κB) and activator protein-1 (AP-1) are major transcription factors that have been associated with breast cancer metastasis by inducing matrix metalloproteinase-9 (MMP-9) expression. In this study, we investigated the inhibitory effects of guggulsterone isomers (cis or trans) on 12-O-tetradecanoylpho-bol-13-acetate (TPA)-induced MMP-9 expression. Cis-guggulsterone inhibited TPA-induced MMP expression by blocking IκB kinase (IKK)/NF-κB signaling, whereas trans-guggulsterone blocked mitogen-activated protein kinase (MAPK)/AP-1 signaling. Cis-guggulsterone was more potent than trans-guggulsterone in the inhibition of TPA-induced MMP-9 expression and invasion of MCF-7 cells. Furthermore, we found that the combination of these isomers exerted an additive effect on the inhibition of MCF-7 cell invasion. These results suggest that guggulsterone isomers downregulate MMP-9 expression and tumor cell invasion through the isomer-specific suppression of IKK/NF-κB and MAPK/AP-1 activation. In addition, the suppression of MMP-9 expression correlated well with the inhibition of cell invasion.
International Journal of Molecular Medicine 12/2012; · 1.98 Impact Factor
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Bo-Mi Hwang,
Eun-Mi Noh, Jong-Suk Kim,
Jeong-Mi Kim,
Jin-Ki Hwang,
Hye-Kyung Kim,
Jae-Seon Kang,
Do-Sung Kim,
Han-Jung Chae,
Yong-Ouk You,
Kang-Beam Kwon,
Young-Rae Lee
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ABSTRACT: Decursin, a coumarin compound, was originally isolated from the roots of Angelica gigas almost four decades ago, and it was found to exhibit cytotoxicity against various types of human cancer cells and anti-amnesic activity in vivo through the inhibition of AChE activity. However, the anti-skin photoaging effects of decursin have not been reported to date. In the present study, we investigated the inhibitory effects of decursin on the expression of matrix metalloproteinase (MMP)-1 and MMP-3 in human dermal fibroblast (HDF) cells. Western blot analysis and real-time PCR revealed that decursin inhibited the ultraviolet (UV)B-induced expression of MMP-1 and MMP-3 in a dose-dependent manner. Decursin significantly blocked the UVB-induced activation of nuclear factor-κB (NF-κB). However, decursin showed no effect on MAPK or AP-1 activity. In this study, decursin prevented the UVB-induced expression of MMPs via the inhibition of NF-κB activation. In conclusion, decursin may be a potential agent for the prevention and treatment of skin photoaging.
International Journal of Molecular Medicine 12/2012; · 1.98 Impact Factor
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Eun-Kyung Song,
Young-Rae Lee,
Yu-Ri Kim,
Ji-Hyun Yeom,
Chae-Hwa Yoo,
Hyun-Kag Kim,
Hye-Min Park,
Hyung-Sub Kang, Jong-Suk Kim,
Uh-Hyun Kim,
Myung-Kwan Han
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ABSTRACT: Insulin stimulates glucose uptake through the membrane translocation of GLUT4 and GLUT1. Peroxisome proliferator-activated receptor γ (PPARγ) enhances insulin sensitivity. Here, we demonstrate that insulin stimulates GLUT4 and GLUT1 translocation, and glucose uptake, by activating the signaling pathway involving nicotinic acid adenine dinucleotide phosphate (NAADP), a calcium mobilizer, in adipocytes. We also demonstrate that PPARγ mediates insulin sensitization by enhancing NAADP production through upregulation of CD38, the only enzyme identified for NAADP synthesis. Insulin produced NAADP by both CD38-dependent and -independent pathways, whereas PPARγ produced NAADP by CD38-dependent pathway. Blocking the NAADP signaling pathway abrogated both insulin-stimulated and PPARγ-induced GLUT4 and GLUT1 translocation, thereby inhibiting glucose uptake. CD38 knockout partially inhibited insulin-stimulated glucose uptake. However, CD38 knockout completely blocked PPARγ-induced glucose uptake in adipocytes and PPARγ-mediated amelioration of glucose tolerance in diabetic mice. These results demonstrated that the NAADP signaling pathway is a critical molecular target for PPARγ-mediated insulin sensitization.
Cell reports. 11/2012;
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Jeong-Mi Kim,
Eun-Mi Noh,
Kang-Beam Kwon, Jong-Suk Kim,
Yong-Ouk You,
Jin-Ki Hwang,
Bo-Mi Hwang,
Byeong-Soo Kim,
Sung-Hoo Lee,
Seung Jin Lee,
Sung Hoo Jung,
Hyun Jo Youn,
Young-Rae Lee
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ABSTRACT: 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.
Phytomedicine: international journal of phytotherapy and phytopharmacology 08/2012; 19(12):1085-92. · 2.17 Impact Factor
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Chang-Min Lee,
In Duk Jung,
Kyung Tae Noh,
Jun Sik Lee,
Jin Wook Park,
Deok Rim Heo,
Jun Ho Park,
Jeong Hyun Chang,
Il-Whan Choi, Jong-Suk Kim,
Yong Kyoo Shin,
Sung-Joo Park,
Myung-Kwan Han,
Chun Geun Lee,
Won-Kyung Cho,
Yeong-Min Park
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ABSTRACT: The downstream of kinase (DOK)-1 is involved in the protein tyrosine kinase (PTK) pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases.
PLoS ONE 01/2012; 7(4):e34554. · 4.09 Impact Factor
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ABSTRACT: The ADP-ribosyl cyclase CD38 whose catalytic domain resides in outside of the cell surface produces the second messenger cyclic ADP-ribose (cADPR) from NAD(+). cADPR increases intracellular Ca(2+) through the intracellular ryanodine receptor/Ca(2+) release channel (RyR). It has been known that intracellular NAD(+) approaches ecto-CD38 via its export by connexin (Cx43) hemichannels, a component of gap junctions. However, it is unclear how cADPR extracellularly generated by ecto-CD38 approaches intracellular RyR although CD38 itself or nucleoside transporter has been proposed to import cADPR. Moreover, it has been unknown what physiological stimulation can trigger Cx43-mediated export of NAD(+). Here we demonstrate that Cx43 hemichannels, but not CD38, import cADPR to increase intracellular calcium through RyR. We also demonstrate that physiological stimulation such as Fcγ receptor (FcγR) ligation induces calcium mobilization through three sequential steps, Cx43-mediated NAD(+) export, CD38-mediated generation of cADPR and Cx43-mediated cADPR import in J774 cells. Protein kinase A (PKA) activation also induced calcium mobilization in the same way as FcγR stimulation. FcγR stimulation-induced calcium mobilization was blocked by PKA inhibition, indicating that PKA is a linker between FcγR stimulation and NAD(+)/cADPR transport. Cx43 knockdown blocked extracellular cADPR import and extracellular cADPR-induced calcium mobilization in J774 cells. Cx43 overexpression in Cx43-negative cells conferred extracellular cADPR-induced calcium mobilization by the mediation of cADPR import. Our data suggest that Cx43 has a dual function exporting NAD(+) and importing cADPR into the cell to activate intracellular calcium mobilization.
Journal of Biological Chemistry 12/2011; 286(52):44480-90. · 4.77 Impact Factor
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ABSTRACT: Paclitaxel (taxol) has been used for the treatment of various human tumors and is an exceedingly efficient chemotherapy agent against esophageal cancer. However, the precise molecular mechanisms of paclitaxel effects on human esophageal adenocarcinoma cells are not well understood. MTT assay and cell cycle analysis were performed to examine the mechanism of antiproliferative and cell viability effects of paclitaxel in human esophageal adenocarcinoma cancer cells. Western blotting was also used to examine the cell cycle- and apoptosis-related proteins. Paclitaxel inhibited the proliferation of SKGT4 cells in a dose- and time-dependent manner with G2/M arrest. In addition, paclitaxel induced apoptosis through the activation of caspase-3 followed by PARP degradation. In conclusion, our results suggest that paclitaxel leads to mitotic cell cycle arrest following G2/M arrest and induces apoptosis via a caspase-3 pathway in SKGT4 cells.
International Journal of Oncology 12/2011; 39(6):1587-91. · 2.40 Impact Factor
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ABSTRACT: Heme oxygenase-1 (HO-1), an inducible enzyme with broad tissue expression, is wel1-regulated in response to hematopoietic stress and preserves vascular homeostasis. We investigated the involvement of HO-1 in HL-60 cell differentiation. Dimethyl sulfoxide (DMSO) completely decreased HO-1 expression in a time-dependent manner, but clearly induced HL-60 cell differentiation, as evidenced by a marked increase in CD11b expression. Interestingly, zinc protoporphyrin (ZnPP), a strong inhibitor of HO-1, induced HL-60 cell differentiation. In contrast, treatment with cobalt protoporphyrin (CoPP), an activator of HO-1, decreased CD11b expression. Additionally, ZnPP downregulated HO-1 protein expression in HL-60 cells, whereas CoPP induced upregulation. These results suggest that HO-1 might have a negative function in DMSO-induced HL-60 cell differentiation. This study provides the first evidence that HO-1 plays an important role in DMSO-induced HL-60 cell differentiation.
BMB reports 11/2011; 44(11):753-7. · 1.72 Impact Factor
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ABSTRACT: Reactive oxygen species (ROS) are formed as a natural by-product of the normal metabolism of oxygen and have important roles in cell signaling. The aim of this study was to investigate direct effects of ROS on atrial hemodynamics and ANP secretion in isolated perfused beating rat atria with antioxidants. When atria were paced at 1.2 Hz, N-acetyl cystein (antioxidant, NAC), α-lipoic acid (antioxidant), tempol (superoxide dismutase mimic), and apocynin (NADPH oxidase inhibitor; NOX inhibitor) did not affect ANP secretion and atrial contractility. When pacing frequency was increased from 1.2 Hz to 4 Hz, the ANP secretion increased and atrial contractility decreased. H(2)O(2) level was increased in perfusate obtained from atria stimulated by high pacing frequency. NAC, α-lipoic acid and tempol attenuated high pacing frequency-induced ANP secretion but apocynin did not. In contrast, pyrogallol (a superoxide generator) augmented high pacing frequency-induced ANP secretion. NOX-4 protein was increased by high pacing stimulation and in diabetic rat atria. In diabetic rat atria, high pacing frequency caused an increased ANP secretion and a decreased atrial contractility, that were markedly attenuated as compared to control rats. NAC and apocynin reduced high pacing frequency-induced ANP secretion in diabetic rat atria. These results suggest that intracellular ROS formation partly through an increasing NOX activity in response to high pacing frequency is associated with an increased ANP secretion in rat atria.
Peptides 10/2011; 32(12):2467-73. · 2.43 Impact Factor
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Young-Rae Lee,
Eun-Mi Noh,
Ji-Hye Han,
Jeong-Mi Kim,
Jin-Ki Hwang,
Bo-Mi Hwang,
Eun-Yong Chung,
Byeong-Soo Kim,
Sung-Ho Lee,
Seung Jin Lee, Jong-Suk Kim
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ABSTRACT: 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.
European journal of pharmacology 10/2011; 674(2-3):80-6. · 2.59 Impact Factor
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ABSTRACT: Estrogen receptor α (ERα) mediates most of the biological effects of estrogen in mammary epithelial cells and stimulates growth signals involving phosphoinositide-3-OH kinase (PI3K)/Akt in breast cancer cells. Phosphatase and tensin homologue (PTEN) is a critical counter-regulator of PI3K signaling and is thus one of the major tumor suppressors in breast cancer. Inhibition of PI3K with an inhibitor, wortmannin, increased the level of PTEN protein in ERα-positive MCF-7 cells, while levels in ERα-negative MDA-MB 231 cells were not altered. In addition, the level of PTEN protein in MCF-7 cells was significantly lower than that in MDA-MB 231 cells, which correlated with high levels of phospho-Akt and phosphatidylinositol-3,4,5,-trisphosphate (PIP3). However, PTEN mRNA expression as measured by real-time PCR showed no differences in either cell line. Notably, the levels of casein kinase 2 (CK2) and phospho-PTEN (Ser380/Thr382/383) in MCF-7 cells were lower than those in MDA-MB 231 cells, indicating that the down-regulation of PTEN protein in MCF-7 cells is caused by low levels of CK2 expression, leading to accelerated PTEN degradation. Collectively, these results suggest that ERα induces the down-regulation of PTEN through PI3K activation in breast cancer cells.
Molecular Medicine Reports 03/2011; 4(2):215-9. · 0.42 Impact Factor
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ABSTRACT: Chemotherapies for breast cancer generally have strong cellular cytotoxicity and severe side effects. Thus, significant emphasis has been placed on combinations of naturally occurring chemopreventive agents. Silibinin is a major bioactive flavonolignan extracted from milk thistle with chemopreventive activity in various organs including the skin, prostate, and breast. However, the mechanism underlying the inhibitory action of silibinin in breast cancer has not been completely elucidated. Therefore, we investigated the effect of silibinin in MCF-7 human breast cancer cells and determined whether silibinin enhances ultraviolet (UV) B-induced apoptosis.
The effects of silibinin on MCF-7 cell viability were determined using the MTT assay. The effect of silibinin on PARP cleavage, as the hallmark of apoptotic cell death, and p53 protein expression in MCF-7 cells was analyzed using Western blot. The effect of silibinin on UVB-induced apoptosis in MCF-7 cells was analyzed by flow cytometry.
A dose- and time-dependent reduction in viability was observed in MCF-7 cells treated with silibinin. Silibinin strongly induced apoptotic cell death in MCF-7 cells, and induction of apoptosis was associated with increased p53 expression. Moreover, silibinin enhanced UVB-induced apoptosis in MCF-7 cells.
Silibinin induced a loss of cell viability and apoptotic cell death in MCF-7 cells. Furthermore, the combination of silibinin and UVB resulted in an additive effect on apoptosis in MCF-7 cells. These results suggest that silibinin might be an important supplemental agent for treating patients with breast cancer.
Journal of breast cancer. 03/2011; 14(1):8-13.
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Young-Rae Lee,
Eun-Mi Noh,
Hyun Ju Oh,
Hyun Hur,
Jeong-Mi Kim,
Ji-Hey Han,
Jin-Ki Hwang,
Byung-Hyun Park,
Jin-Woo Park,
Hyun Jo Youn,
Sung Hoo Jung,
Byeong-Soo Kim,
Ji-Youn Jung,
Sung-Ho Lee,
Chang-Sik Park, Jong-Suk Kim
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ABSTRACT: 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.
Biochemical and Biophysical Research Communications 01/2011; 405(4):552-7. · 2.48 Impact Factor
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Hyeong-Jin Kim,
Sang-Ki Kim,
Byeong-Soo Kim,
Seung-Ho Lee,
Young-Seok Park,
Byung-Kwon Park,
So-Jung Kim,
Jin Kim,
Changsun Choi, Jong-Suk Kim,
Sung-Dae Cho,
Ji-Won Jung,
Kyong-Hwan Roh,
Kyung-Sun Kang,
Ji-Youn Jung
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ABSTRACT: 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.
Journal of Agricultural and Food Chemistry 08/2010; 58(15):8643-50. · 2.82 Impact Factor
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ABSTRACT: The tumor suppressor protein, PTEN (phosphatase and tensin homologue), has been reported to play a crucial role in a variety of tumor cells. Recent studies indicate that the transcription factor, PPARgamma (peroxisome proliferator-activated receptor gamma) up-regulates PTEN expression transcriptionally through the binding of two response elements in the genomic sequence upstream of PTEN in tumor cells. Here, we determined the PTEN and PPARgamma expression in human leiomyomas, and whether estrogen can change their protein expressions in cultured leiomyoma cells. Immunohistochemical staining and Western blot analysis revealed that PTEN protein levels in leiomyomas were higher than that the adjacent normal myometrial tissues, which was paralleled with decrease in phospho-Akt (ser-473) and phosphatidylinositol 3,4,5-tris phosphate (PIP3) level. Interestingly, leiomyomas exhibit high PPARgamma expression compared to the adjacent normal myometrial tissues. In addition, we found that 17beta-estradiol (E2) significantly stimulated PTEN and PPARgamma expression in cultured leiomyoma cells, but did not change both protein levels in normal cells. This report shows the first evidence that PTEN and PPARgamma are up-regulated in leiomyoma tissues, and estrogen stimulates expression of PTEN and PPARgamma in leiomyoma cells, but not in normal cells.
International Journal of Oncology 04/2010; 36(4):921-7. · 2.40 Impact Factor
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Eun-Mi Noh,
Hyun Jo Youn,
Sung Hoo Jung,
Ji-Hey Han,
Youg-Ju Jeong,
Eun-Yong Chung,
Ji-Youn Jung,
Byeong-Soo Kim,
Sung-Ho Lee,
Young-Rae Lee, Jong-Suk Kim
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ABSTRACT: Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in breast cancer cell invasion. NF-kappaB and AP-1 are known to induce MMP-9 expression. We investigated whether cordycepin, an NF-kappaB or AP-1 inhibitor, can modulate MMP-9 expression and cell invasion in MCF-7 cells. Toxicity of cordycepin was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MMP-9 expression was determined by real-time PCR, Zymography, and Western blot analysis. AP-1 activation was assayed by electrophoretic mobility shift assay (EMSA). MAPK signaling was evaluated by Western blotting with specific p-ERK, and ERK, p-p38, p38, p-JNK, JNK antibodies. Cordycepin suppressed AP-1 activation, but not NF-kappaB activation in 12-O-tetradecanoylpho-bol-13-acetate (TPA)-treated MCF-7 cells. Cordycepin inhibits TPA-induced MMP-9 expression and cell invasion by suppressing AP-1 activation. Also, cordycepin suppressed the MAPK signaling pathway. Cordycepin is a potent inhibitor of TPA-induced MMP-9 expression and blocks strongly the ability of AP-1 activation via MAPK signaling pathway in MCF-7 cells.
International Journal of Molecular Medicine 02/2010; 25(2):255-60. · 1.98 Impact Factor
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Hyun Jang,
Hyo-Seung Kim,
Seung-Cheol Moon,
Young-Rae Lee,
Kang-Yeoul Yu,
Byeong-Kil Lee,
Hyun Zo Youn,
Young-Ju Jeong,
Byeong-Soo Kim,
Sung-Ho Lee, Jong-Suk Kim
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ABSTRACT: Lipopolysaccharide (LPS), found in the outer membrane of Gram negative bacteria, only exerts its toxic effects when in free form. LPS has three major parts, lipid A, the toxic component, along with a core polysaccharide and O-specific polysaccharide. LPS monomers are known to have molecular masses between 10 to 30 kDa. Under physiological conditions, LPS exists in equilibrium between monomer and vesicle forms. LPS removal by 100 kDa ultrafiltration was more efficient (99.6% of LPS removed) with a low concentration of protein (2.0 mg/ml) compared to a high concentration (20.1 mg/ml). In the presence of different detergents (0.5% Tween 20, 1.0% taurodeoxycholate and 1.0% Triton X-100), LPS removal was more efficient at low protein concentrations (2.0 mg/ml) compared to high protein concentrations (20.1 mg/ml).
BMB reports 08/2009; 42(7):462-6. · 1.72 Impact Factor
