Chang-Hee Kang

Jeju National University, Tse-tsiu, Jeju, South Korea

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Publications (18)39.58 Total impact

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    ABSTRACT: Little is known about whether trans-isoferulic acid (TIA) regulates the production of lipopolysaccharide (LPS)-induced proinflammatory mediators. Therefore, we examined the effect of TIA isolated from Clematis mandshurica on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in BV2 microglial cells. We found that TIA inhibited the production of LPS-induced NO and PGE2 without accompanying cytotoxicity in BV2 microglial cells. TIA also downregulated the expression levels of specific regulatory genes such as inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) by suppressing LPS-induced NF-κB activity via dephosphorylation of PI3K/Akt. In addition, we demonstrated that a specific NF-κB inhibitor PDTC and a selective PI3K/Akt inhibitor, LY294002 effectively attenuated the expression of LPS-stimulated iNOS and COX-2 mRNA, while LY294002 suppressed LPS-induced NF-κB activity, suggesting that TIA attenuates the expression of these proinflammatory genes by suppressing PI3K/Akt-mediated NF-κB activity. Our results showed that TIA suppressed NO and PGE2 production through the induction of nuclear factor-2-erythroid 2-related factor 2 (Nrf2)-dependent heme oxygenase-1 (HO-1). Taken together, our data indicate that TIA suppresses the production of proinflammatory mediators such as NO and PGE2, as well as their regulatory genes, in LPS-stimulated BV2 microglial cells, by inhibiting PI3K/Akt-dependent NF-κB activity and enhancing Nrf2-mediated HO-1 expression.
    International immunopharmacology 11/2013; · 2.21 Impact Factor
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    ABSTRACT: Abnormal nitrosative stress-induced neuroinflammation is implicated in the pathogenesis of neurodegenerative diseases. Therefore, it has been thought that nitric oxide (NO) production is a good therapeutic target. In this sense, quercetin is a good chemopreventive component, because it has free radical-scavenging and anti-inflammatory activities. However, explicit mechanisms are not clear in the lipopolysaccharide (LPS)-stimulated BV2 microglial cell line. Here, we found that quercetin significantly suppressed LPS-induced NO production and inducible NO synthase (iNOS) expression. Notably, quercetin inhibited nuclear factor-κB (NF-κB) activation by inhibiting degradation of the inhibitor of kappa Bα (IκBα) in LPS-stimulated BV2 microglial cells corresponding to the inhibitory effect of specific NF-κB inhibitors, namely proteasome inhibitor I (PSI) and MG132. Quercetin caused significant increases in the levels of heme oxgenase-1 (HO-1) mRNA and protein. Notably, treatment with an HO-1 inducer, cobalt protoporphyrin (CoPP), significantly diminished LPS-stimulated NO production. Additionally, quercetin induced the specific DNA-binding activity of nuclear factor-2-erythroid 2-related factor 2 (Nrf2), and siRNA-mediated knockdown of Nrf2 expression reduced the inhibitory effect of quercetin on LPS-stimulated NO production by inhibiting HO-1 expression, indicating that quercetin regulated NO production by inducing Nrf2-mediated HO-1 expression. Therefore, quercetin has the potential to decrease nitrosative stress by suppressing NF-κB activation and inducing Nrf2-mediated HO-1 expression.
    International immunopharmacology 09/2013; · 2.21 Impact Factor
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    ABSTRACT: Schisandra chinensis has a long-standing history of medicinal use as a tonic, a sedative, an anti-tussive, and an anti-aging drug. Nevertheless, the antagonistic effects of S. chinensis against lipopolysaccharide (LPS)-stimulated responses have not yet been studied. In this study, we investigated whether water extract of S. chinensis fruit (WESC) has the ability to attenuate the expression of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-α (TNF-α) in LPS-stimulated RAW 264.7 macrophage cells. WESC inhibited the expression of LPS-induced pro-inflammatory mediators, namely, NO, PGE2, and TNF-α. Furthermore, gene expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α was inhibited both at mRNA and protein synthesis levels, without any cytotoxic effect. Moreover, WESC significantly suppressed LPS-induced DNA-binding activity of NF-κB by inhibiting degradation of IκBα. It was found that pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, downregulates the expression of these pro-inflammatory genes to be closely regulated by NF-κB activity. Furthermore, we found that WESC retains dephosphorylation of Akt in response to LPS, and consequently suppressed the DNA-binding activity of NF-κB in RAW 264.7 macrophage cells. LY294002, a specific Akt inhibitor, attenuated LPS-induced pro-inflammatory gene expression via suppression of NF-κB activity. Taken together, our results indicate that WESC downregulates the expression of pro-inflammatory genes involved in the synthesis of NO, PGE2, and TNF-α in LPS-stimulated RAW 264.7 macrophage cells by suppressing Akt-dependent NF-κB activity.
    Environmental toxicology and pharmacology. 04/2013; 36(2):256-264.
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    ABSTRACT: In this study, we found that 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone (5HHMF) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of inducible NO synthase (iNOS) in BV2 microglia. In addition, 5HHMF blocked LPS-induced phosphorylation of IκB, resulting in suppression of the nuclear translocation of nuclear factor-κB (NF-κB) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression. Pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-κB activity. Thus, we found that 5HHMF enhances heme oxygenase-1 (HO-1) expression via nuclear factor-erythroid 2-related factor 2 (Nrf2) activation. In addition, cobalt protoporphyrin (CoPP), a specific HO-1 inducer, predominantly suppressed LPS-induced NO production. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, showed a partial suppressive effect of 5HHMF on LPS-induced NO production. Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity. Taken together, our findings indicate that 5HHMF suppresses NO production through modulation of iNOS, consequently suppressing NF-κB activity and induction of Nrf2-dependent HO-1 activity.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 03/2013; · 2.99 Impact Factor
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    ABSTRACT: β-Ionone, a precursor of carotenoids, possesses a variety of biological properties such as anti-cancerous, anti-mutagenic and anti-microbial activity. Nevertheless, anti-inflammatory effects of β-ionone remain unknown. In this study, we investigated whether ION attenuates the expression of lipopolysaccharide (LPS)-induced pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α) in BV2 microglia cells. Our data showed that β-ionone significantly inhibits secretion of NO, PGE2 and TNF-α. β-Ionone also inhibits the expression of inducible NO synthesis (iNOS), cyclooxygenase-2 (COX-2) and TNF-α protein and their mRNA in LPS-stimulated BV2 microglia cells. In addition, β-ionone significantly reduced DNA-binding activity of nuclear factor-κB (NF-κB) through suppression of nuclear translocation of p50 and p65. We showed that NF-κB inhibitor N-acetyl-L-cysteine (NAC) effectively attenuates the expression of LPS-stimulated iNOS, COX-2 and TNF-α. We also found that LPS-induced NF-κB activation is significantly regulated through inhibition of Akt phosphorylation in the presence of β-ionone. Finally, we showed that β-ionone substantially inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, p38 and JNK, which are closely related to regulation of pro-inflammatory mediator secretion. Taken together, these data imply that β-ionone regulates LPS-induced NF-κB-dependent inflammatory pathways through suppression of Akt and MAPK activation.
    Toxicology in Vitro 03/2013; 27(2):782–787. · 2.65 Impact Factor
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    ABSTRACT: Piceatannol has potent anti-inflammatory, immunomodulatory, anticancer and antiproliferative effects. However, little is known about the mechanism by which piceatannol inhibits invasion and metastasis. The aim of the current study was to investigate the effects of piceatannol on the expression of matrix metalloproteinase-9 (MMP-9) in DU145 human prostate cancer cells. The results revealed that MMP-9 activity was significantly increased in response to tumor necrosis factor-α (TNF-α). However, treatment with piceatannol reversed TNF-α- and MMP-9-induced gelatin zymography and its gene expression. In addition, a Matrigel invasion assay determined that piceatannol reduces the TNF-α-induced invasion of DU145 cells. Nuclear factor-κ B (NF-κB) is a significant transcription factor that regulates numerous genes involved in tumor cell invasion and metastasis. Therefore, whether piceatannol acts on NF-κB to regulate MMP-9 gene expression was analyzed. The results revealed that piceatannol attenuates MMP-9 gene expression via the suppression of NF-κB activity. Using a specific NF-κB inhibitor, pyrrolidine dithiocarbamate, it was confirmed that TNF-α-induced MMP-9 gene expression is primarily regulated by NF-κB activation. Piceatannol inhibited NF-κB activity by suppressing nuclear translocation of the NF-κB p65 and p50 subunits. Furthermore, TNF-α-induced Akt phosphorylation was significantly downregulated in the presence of piceatannol. The Akt inhibitor LY294002 caused a significant decrease in TNF-α-induced NF-κB activity and MMP-9 gene expression. Overall, these data suggest that piceatannol inhibits TNF-α-induced invasion by suppression of MMP-9 activation via the Akt-mediated NF-κB pathway in DU145 prostate cancer cells.
    Oncology letters 01/2013; 5(1):341-347. · 0.24 Impact Factor
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    ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for new cancer therapeutics. However, resistance to TRAIL in some cancers remains a current problem in recent. The protein-folding compartment of the endoplasmic reticulum (ER) is particularly sensitive to disturbances, which, if severe, may trigger apoptosis. Therefore, we examined whether verrucarin A (VA) sensitize TRAIL-induced apoptosis in cancer cells by induction of ER stress. We first found that VA induces a major molecule of ER stress, CCAAT/enhancer binding protein homologous protein (CHOP)-dependent DR5 induction and subsequently increases TRAIL-induced cleavage of caspases and PARP in TRAIL-resistant Hep3B cells. Importantly, the transient knockdown using siRNA for CHOP abrogated VA-induced DR5 expression and attenuated TRAIL-induced apoptosis. Treatment with VA also increased the levels of phosphorylation of eukaryotic translation initiation factor-2α (eIF2α), which is a common cellular response of ER stress. Furthermore, salubrinal, a specific eIF2α phosphorylation-inducing agent, increased CHOP and DR5 expression in the presence of VA. In contrast, transfection of mutant-eIF2α significantly reversed VA-induced apoptosis with downregulation of CHOP-dependent DR5 expression. Therefore, VA-induced eIF2α phosphorylation seemed to be important for CHOP and DR5 upregulation and TRAIL-induced apoptosis. In addition, generation of reactive oxygen species (ROS) is an effector molecular in sensitization of VA-induced ER stress. We concluded that VA triggers TRAIL-induced apoptosis by eIF2α/CHOP-dependent DR5 induction via ROS generation.
    Toxicology in Vitro 09/2012; · 2.65 Impact Factor
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    ABSTRACT: Since the anti-inflammatory effect of caffeine is unclear in microglial cells, we performed whether caffeine attenuates the expression of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Caffeine substantially suppressed the LPS-induced pro-inflammatory mediators nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor-α (TNF-α) in BV2 microglial cells. These effects resulted from the inhibition of their regulatory genes inducible NO synthase (iNOS), cycloxygenase-2 (COX-2) and TNF-α. In addition, caffeine significantly decreased LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB) by suppressing the nuclear translocation of p50 and p65 subunits. A specific NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), attenuated the LPS-induced expression of iNOS, COX-2 and TNF-α genes. In addition, we elucidated that inhibition of Akt phosphorylation plays a crucial role in caffeine-mediated NF-κB regulation in LPS-stimulated BV2 microglial cells. Caffeine also attenuated the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and a specific inhibitor of ERK, PD98059, subsequently downregulated the expression of the pro-inflammatory genes iNOS, COX-2 and TNF-α. Taken together, our data indicate that caffeine suppresses the generation of pro-inflammatory mediators, such as NO, PGE(2) and TNF-α as well as their regulatory genes in LPS-stimulated BV2 microglial cells by inhibiting Akt-dependent NF-κB activation and the ERK signaling pathway.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 09/2012; 50(12):4270-4276. · 2.99 Impact Factor
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    Food and Chemical Toxicology. 06/2012; 50(6):2250.
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    ABSTRACT: Recent studies have shown that apigenin (4',5,7-trihydroxyflavone inhibits human malignant cancer cell growth through cell cycle arrest and apoptosis. However, the underlying relationship between apoptosis and telomerase activity in response to apigenin exposure is not well understood. In this study, we found that apigenin significantly induces direct cytotoxicity in human leukemia cells (U937, THP-1 and HL60) through activation of the caspase pathway. As we presumed, treatment with apigenin was found to increase the level of intracellular reactive oxygen species (ROS), whereas pretreatment with antioxidants, N-acetyl-cysteine (NAC) or glutathione (GSH), completely attenuated ROS generation. Surprisingly, these antioxidants did not promote recuperation from apigenin-induced cell death. We further showed that apigenin downregulates telomerase activity in caspase-dependent apoptosis and observed that apigenin dosing results in downregulation of telomerase activity by suppression of c-Myc-mediated telomerase reverse transcriptase (hTERT) expression. In addition, treatment of apigenin-dosed cells with the two antioxidants did not restore telomerase activity. Taken together, this data suggests that ROS is not essential for suppression of apigenin-mediated apoptosis associated with the activation of caspases and regulation of telomerase activity via suppression of hTERT. We conclude that apigenin has a direct cytotoxic effect and the loss of telomerase activity in leukemia cells.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2012; 50(8):2605-11. · 2.99 Impact Factor
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    ABSTRACT: The anti-apoptotic oncogene K-RAS is hypothesized to increase the antioxidant status of cells, thereby protecting them from generation of reactive oxygen species (ROS). Therefore, we examined whether K-RAS overcomes hydrogen peroxide (H2O2)-mediated apoptosis in the human fetal prostate epithelial cell 267B1. In this study, we found that treatment of 267B1 cells with H2O2 resulted in significant reduction of cell growth, which was associated with cytochrome-c release and caspase-3 activation. However, mutated K-RAS transformation (268B1/K-RAS) rendered 267B1 cells reduction of the resistance to H2O2-induced apoptosis through suppression of ROS generation. In addition, we analyzed profiling of gene expression in K-RAS transformation and found that gamma-glutamyltransferase 2 (GGT2) most highly expressed. Transient knockdown of K-RAS resulted in a significant downregulation of GGT gene expression. We also revealed that expression of GGT2 gene is closely regulated by the ERK signal pathway in 267B1/K-RAS cells. In addition, the anti-apoptotic effect of mutated K-RAS was attenuated by treatment with GGT2 RNA interference through inhibition of ROS generation, suggesting that mutated K-RAS mediates resistance to H2O2-induced apoptosis through GGT2 activation. These results importantly provide mechanistic insights on the anti-apoptotic activity of mutated K-RAS.
    Toxicology in Vitro 04/2012; 26(3):429-34. · 2.65 Impact Factor
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    ABSTRACT: Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various malignant cells, several cancers including human hepatocellular carcinoma (HCC) exhibit potent resistance to TRAIL-induced cell death. The aim of this study is to evaluate the anti-cancer potential of capsaicin in TRAIL-induced cancer cell death. As indicated by assays that measure phosphatidylserine exposure, mitochondrial activity and activation of caspases, capsaicin potentiated TRAIL-resistant cells to lead to cell death. In addition, we found that capsaicin induces the cell surface expression of TRAIL receptor DR5, but not DR4 through the activation Sp1 on its promoter region. Furthermore, we investigated that capsaicin-induced DR5 expression and apoptosis are inhibited by calcium chelator or inhibitors for calmodulin-dependent protein kinase. Taken together, our data suggest that capsaicin sensitizes TRAIL-mediated HCC cell apoptosis by DR5 up-regulation via calcium influx-dependent Sp1 activation.
    Toxicology and Applied Pharmacology 12/2011; 259(1):87-95. · 3.98 Impact Factor
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    ABSTRACT: The methanol extract of Codium fragile (MECF) has been reported to possess bioactive properties such as antidegranulation in eosinophils, as well as anti-edema, antibacterial, and antiviral activities. However, little is known about the molecular effects of MECF on lipopolysaccharide (LPS)-induced inflammation. Therefore, we investigated whether MECF affects the expression of inflammatory mediators in LPS-stimulated RAW 264.7 cells. To evaluate the anti-inflammatory effects of MECF, the cells were pretreated with MECF for 1 hour and then cultured with LPS for 24 hours. Our results indicate that MECF significantly attenuated secretion of LPS-induced inflammatory mediators nitric oxide (NO), prostaglandin E(2) (PGE(2)), and tumor necrosis factor (TNF)-α in RAW 264.7 cells. Additionally, LPS-induced mRNA and protein expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α was decreased by pretreatment with MECF. These data indicate that MECF attenuates the expression of these inflammatory mediators at the transcriptional level. Therefore, we also investigated the effects of MECF on nuclear factor-κB (NF-κB) activity, which may be an important transcriptional factor for regulating the expression of iNOS, COX-2, and TNF-α mRNA. Our results showed that MECF reduced LPS-induced NF-κB activity via the suppression of nuclear translocation of the p50 and p65 NF-κB subunits and degradation of inhibitor of κB. In conclusion, we propose that MECF treatment down-regulates the expression and secretion of LPS-induced inflammatory mediators by inhibiting NF-κB activity.
    Journal of medicinal food 11/2011; 15(1):44-50. · 1.39 Impact Factor
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    ABSTRACT: Our previous study showed that the exopolysaccharide (EPS) of Laetiporus sulphureus var. miniatus was well characterized and prevented cell damage in streptozotocin-induced apoptosis. However, little is known about the molecular mechanisms underlying its anti-inflammatory effects. Therefore, we attempted in this study to determine whether EPS induces a significant inhibition of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV2 microglia cells. Our results showed that EPS significantly inhibited LPS-induced pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E(2) (PGE(2)), and tumor necrosis factor-α (TNF-α), without any significant cytotoxicity. EPS also downregulated mRNA and protein expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α in LPS-induced BV2 microglia cells. Our data also revealed that EPS treatment significantly reduced translocation of nuclear factor-κB (NF-κB) subunit p65 and its DNA-binding activity in LPS-stimulated BV2 microglia cells. Furthermore, we confirmed by using proteasome inhibitor N-acetyl-l-cysteine (NAC), that the inhibition of NF-κB activity influenced the expression of pro-inflammatory genes in LPS-induced BV2 microglia cells. As expected, NAC suppressed the expression of iNOS, COX-2, and TNF-α by blocking proteasome-mediated degradation. Taken together, our data indicate that EPS inhibits the expression of pro-inflammatory mediators by suppressing NF-κB activity.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 08/2011; 49(11):2758-64. · 2.99 Impact Factor
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    ABSTRACT: Although piceatannol (PIC) is known to mediate anti-cancer, anti-inflammatory, and anti-oxidant activities, little is known about the mechanism of PIC in terms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. In this study, we examined whether combined treatment with PIC and TRAIL synergistically induces apoptosis in THP-1 leukemia cells. Results indicate that PIC substantially enhances TRAIL-induced cell death including DNA fragmentation and poly(ADP-ribose) polymerase cleavage. Consistent with TRAIL-induced apoptosis, PIC significantly increased the mRNA and protein expression levels of DR5, a death receptor of TRAIL. Further, PIC enhanced DR5 promoter activity via Sp1 activation. Interestingly, the DR5 chimera antibodies significantly suppressed PIC and TRAIL-mediated apoptosis. The inhibitor of ERK also decreased PIC and TRAIL-induced apoptosis by blocking DR5 expression. In conclusion, our results suggest that PIC sensitizes TRAIL-induced-apoptosis via Sp1- and ERK-dependent DR5 up-regulation.
    Toxicology in Vitro 12/2010; 25(3):605-12. · 2.65 Impact Factor
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    ABSTRACT: Up-regulation of telomerase activity is associated with immortalization and unlimited cell division in most cancer cells. Therefore, telomerase represents a particularly attractive target for anticancer therapy. Recent reports have suggested that beta-lapachone (LAPA), the product of the South American Tabebuia avellanedae tree, inhibits growth of tumor cells. However, the underlying relationship between telomerase activity and apoptosis in response to LAPA exposure in leukemia cells remains poorly understood. In this study, we confirmed that LAPA treatment induces direct cytotoxicity in human leukemia cells (U937, K562, HL60, and THP-1) through activation of caspase-3 and subsequent cleavage of poly(ADP-ribose) polymerase. The observed induction of cell death was associated with decreased telomerase activity, which was ascribed to down-regulation of telomerase reverse transcriptase. Additionally, overexpression of anti-apoptotic Bcl-2 could not overcome the induction of apoptosis or the decreased telomerase activity in response to treatment of U937 cells with LAPA. We conclude that LAPA has a direct cytotoxic effect and the loss of telomerase activity in leukemia cells.
    Journal of medicinal food 06/2010; 13(3):481-8. · 1.39 Impact Factor
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    ABSTRACT: beta-Ionone (ION), an end-ring analogue of beta-carotenoid, has been known to inhibit tumor cell growth and induce apoptosis in various types of cancer cells. Nevertheless, its apoptosis-related molecular mechanisms remain unclear. Here, we first investigated the molecular mechanisms by which ION sensitizes cancer cells to the therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Notably, treatment with subtoxic concentrations of ION and TRAIL effectively inhibited cell viability in the hepatocellular carcinoma cell line Hep3B and other cancer cell lines such as colon carcinoma cell line HCT116 and leukemia cell line U937. Combined treatment with ION and TRAIL was also more effective in inducing DR5 expression, caspase activities, and apoptosis than treatment with either agent alone. ION-mediated sensitization to TRAIL was efficiently reduced by treatment with a chimeric blocking antibody or small interfering RNA specific for DR5. Electrophoretic mobility shift assay and a chromatin immunoprecipitation assay confirmed that ION treatment upregulates the binding of transcription factor Sp1 to its putative site within the DR5 promoter region, suggesting that Sp1 is an ION-responsive transcription factor. In addition, ION significantly increased hepatocellular carcinoma cell sensitivity to TRAIL by abrogating TRAIL-induced NF-kappaB activation and decreasing the expression of antiapoptotic proteins such as XIAP and IAP-1/2. Taken together, these data suggest that ION is a useful agent for TRAIL-based cancer treatments. Mol Cancer Ther; 9(4); 833-43. (c)2010 AACR.
    Molecular Cancer Therapeutics 03/2010; 9(4):833-43. · 5.60 Impact Factor
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    ABSTRACT: A c-Jun N-terminal kinase inhibitor, SP600125, strongly inhibits cell proliferation in many human cancer cells by blocking cell-cycle progression and inducing apoptosis. Despite extensive study, the mechanism by which SP600125 inhibits mitosis-related effects in human leukemia cells remains unclear. This present paper aims to investigate the effects of SP600125 on the inhibition of cell proliferation and the cell cycle and on microtubule (MT) dynamics in vivo and in vitro. Treatment of synchronized leukemia cells with varying concentrations of SP600125 has resulted in significant G2/M cell cycle arrest with elevated p21 and phosphorylation of histone H3 within 24 h and endoreduplication (END) with elevated Cdk2 protein at 48 h. SP600125 has also