ß-Dihydroartemisinin-Emodin Promotes Apoptosis by Activating Extrinsic and Intrinsic Pathways in Human Liver Cancer Cells.

Natural products isolated from Chinese herbs are promising anticancer therapeutic agents. In the current study, we explored the anticancer effect of a novel drug compound, ß-dihydroartemisinin-emodin (ß-DHA-emodin), on human liver cancer HepG-2 cells. The drug showed high suppressive activity against the proliferation of HepG-2 cells by inhibiting Ki-67 expression. ß-DHA-emodin treatment increased the apoptotic ratio of HepG-2 cells by preventing cell cycle progression from the G1 phase to the S phase. Cells treated with ß-DHA-emodin showed typical apoptotic morphological changes. ß-DHA-emodin also upregulated the expression of caspase-3/8/9 and Bax and downregulated the expression of Bcl-2. ß-DHA-emodin inhibited HepG-2 migration by decreasing the expression of Survivin. These results indicate that ß-DHA-emodin may be an efficacious apoptotic inducer in HepG-2 cells.

Cytotoxic fraction from Artemisia sacrorum Ledeb. against three human cancer cell lines and separation and identification of its compounds.

Artemisia sacrorum Ledeb. was extracted by 95% ethanol and water, respectively. By partitioning the 95% ethanol extract successively with different solvents and separating the water extract by macroporous resin, nine separate parts were obtained. According to the results of in vitro experiments, the CH2Cl2 (dichloromethane) fraction showed the most pronounced cytotoxic activity against HepG2, HT-29 and MCF-7 cells, with EC50 values 122.35, 49.76 and 28.51 µg mL⁻¹, respectively, at 48 h. Following this, the compounds of the CH2Cl2 fraction were separated and identified. Ten compounds were isolated from A. sacrorum Ledeb. and identified by spectral analysis. Four compounds, including acacetin, were isolated for the first time from A. sacrorum Ledeb.

Monitoring of PCBs at facilities related with PCB-containing products and wastes in South Korea.

Polychlorinated biphenyl (PCB) contents were analyzed in samples collected from facilities related to PCB-containing products or wastes in South Korea. Average concentrations of the atmospheric Σ(209) PCBs were 7420 (37.0-104,048)pgm(-3) and 16.8 (ND-34.2 )fg WHO-TEQ m(-3) in indoor air samples; and 1670 (106-13,382)pgm(-3) and 5.64 (ND-36.0) fg WHO-TEQ m(-3) in outdoor air samples. The highest levels were observed in indoor air samples from disposal facilities (7336-104,048 pg m(-3)), followed by production (330-25,057 pg m(-3)), recycling, and storage facilities, indicating that PCB emissions from PCB-containing products and wastes remains very high and the facilities related with those may be an important source to atmospheric PCBs. Principal component analysis of PCB profiles showed that the homologue patterns of PCBs in outdoor and indoor air samples collected from the facilities were similar to those of boundary air samples and PCB commercial products, e.g. Aroclor 1016, 1221, 1232 and 1242. Evaluation of the PCB mass balance in a facility, dismantling and solvent-washing PCB-contaminated transformers, showed that of the total PCBs treated in this facility, approximately 0.0022% was emitted to the atmosphere, and most was transferred to waste oil for disposal by incineration or chemical methods.

Synthesis and antiproliferative activity of 1,4-bis(dimethylamino)-9,10-anthraquinone derivatives against P388 mouse leukemic tumor cells.

A series of 2-substituted-1,4-bis(dimethylamino)-9,10-anthraquinone derivatives were synthesized and their in vitro antiproliferative activities against p388 mouse leukemic tumor cells were evaluated. In addition, the effect of substituents on the phenyl ring was investigated. Among the derivatives tested, seven showed a high antiproliferative effect and three showed a moderate effect. In addition, introduction of a series of substituted phenyl groups into 1,4-bis(dimethylamino)-9,10-anthraquinone at 2-position were shown to enhance its antiproliferative activity. The antiproliferative activity also increased upon substitution of the benzene ring by an electron donating group such as an amine or methoxyl group.

Nationwide monitoring of atmospheric PCDD/Fs and dioxin-like PCBs in South Korea.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) were measured in ambient air samples collected from different parts of South Korea in 2008, and the measured levels were used for assessing the spatial and temporal distribution of atmospheric PCDDFs and DL-PCBs in South Korea. The average concentrations of atmospheric PCDD/Fs and DL-PCBs among the 37 sites were 28 fg I-TEQ m(-3) (ND~617) and 1 fg WHO-TEQ m(-3) (ND~0.016). Elevated atmospheric levels of PCDD/Fs and DL-PCBs observed at residential/industrial sites and in the north-west of Korea, indicated a potential contribution and impacts of anthropogenic sources of PCDD/Fs and DL-PCBs. These levels were similar or lower than those previously reported in other ambient air surveys. Average concentrations of PCDD/Fs showed small seasonal variations (ANOVA analysis, p=0.144). The highest concentrations of PCDD/Fs were observed during winter, followed by spring, autumn and summer. Atmospheric PCDD/Fs and DL-PCBs in South Korea rapidly decreased during the last 10 years (1998-2008), demonstrating the efficiency of stricter regulations and the application of best available technologies/best environmental practices at emission sources. Comparison of the congener profiles and principal component analysis showed that current atmospheric PCDD/Fs are mostly influenced by industrial sources and PCBs from old commercial PCB uses. Nationwide POPs monitoring will continue and allows an effective evaluation of the implementation of the Stockholm Convention on POPs.

Detection of Dechlorane Plus in fish from urban-industrial rivers.

A highly chlorinated flame retardant, Dechlorane Plus (DP), was measured in five fish species collected in 2008 from 22 river sites across South Korea. The sites consisted of 15 urban-industrial areas, three rural-industrial areas, and four rural rivers. Both syn- and anti-DP isomer were consistently detected in all fish samples regardless of sampling sites and fish species. DP has become a widespread environmental pollutant in South Korea. Concentrations of summation operatorDP isomers ranged from 0.61 to 126ngg(-1) lipid, with a mean concentration of 24.5ngg(-1) lipid. The mean summation operatorDP concentrations in the 15 urban sites (36.1+/-35.3ngg(-1) lipid) were approximately 25 times greater than those measured in the rural sites (1.4+/-1.0ngg(-1) lipid). The summation operatorDP concentrations in this study exceeded those determined in fish from the Great Lakes. DP exposure to fish is related to urbanization activity. Specific urban areas could be significant source areas of DP exposure, even in the absence of a local DP manufacturing facility. Concentrations of syn- and anti-DP isomer ranged from 0.17 to 30ngg(-1) lipid and 0.44 to 97ngg(-1) lipid, respectively. The anti-DP isomer was dominant in all samples. However, the mean f(anti) value for urban-industrial samples (0.67+/-0.060) was significantly lower than that of the technical DP standard (f(anti)=0.75; p=0.032). This observation supports that DP isomers exhibit different bioaccumulation behaviors and that syn-DP isomer more easily accumulates in biota samples than anti-DP isomer does.

An active part of Artemisia sacrorum Ledeb. attenuates hepatic lipid accumulation through activating AMP-activated protein kinase in human HepG2 cells.

Artemisia sacrorum Ledeb. (Compositae) (ASL) is a traditional Chinese medicine used to treat different hepatic diseases. However, a hypolipidemic effect of ASL on fatty liver disease has not been reported. Therefore, we investigated whether 95% ethanol eluate (EE), an active part of ASL, would attenuate hepatic lipid accumulation in human HepG2 cells by activating AMP-activated protein kinase (AMPK). Significant decreases in triglyceride levels and increases in AMPK and acetyl-CoA carboxylase (ACC) phosphorylation were observed when the cells were treated with 95% EE. EE down-regulated the lipogenesis gene expression of sterol regulatory element-binding protein 1c (SREBP1c) and its target genes, such as fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1), in a time- and dose-dependent manner. In contrast, the lipolytic gene expression of peroxisome proliferator-activated receptor alpha (PPAR-alpha) and CD36 increased in a time- and dose-dependent manner. These effects were abolished by pretreatment with compound C, an AMPK inhibitor. However, there were no differences in the gene expression of SREBP2, low density lipoprotein receptor (LDLR), hydroxymethyl glutaryl CoA reductase (HMG-CoA), or glucose transporter 2 (GLUT2). At the same time, 95% EE significantly increased the gene expression of acyl CoA oxidase (ACOX) in a time- and dose-dependent manner. Thus, AMPK mediated 95% EE induced suppression of SREBP1c and activation of PPAR-alpha respectively. These finding indicate that 95% EE attenuates hepatic lipid accumulation through AMPK activation and may be active in the prevention of serious diseases such as fatty liver, obesity, and type-2 diabetic mellitus.

Hepatoprotective effects of an active part from Artemisia sacrorum Ledeb. against acetaminophen-induced toxicity in mice.

AIMS OF STUDY: Although Artemisia sacrorum Ledeb. (Compositae) has long been used as one kind of oriental folk medicine to treat some liver diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. This study was designed to investigate the hepatoprotective effects of 50% ethanol eluate precipitation of Artemisia sacrorum Ledeb. (EEP) on acetaminophen (APAP)-induced toxicity in mice. MATERIALS AND METHODS: The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-alpha (TNF-alpha) levels in mouse sera, and glutathione (GSH), malondialdehyde (MDA) in mouse liver tissues were measured. In addition, apoptosis and necrosis were evaluated by liver histopathological analysis and DNA laddering. Moreover, caspase-3 and -8 protein expressions in mouse livers were observed by Western blot analysis. RESULTS: Pretreated with EEP prior to the administration of APAP significantly prevented the increases of AST, ALT, and TNF-alpha levels in sera, and suppressed the GSH depletion, MDA accumulation in liver tissues markedly. In addition, EEP prevented APAP-induced apoptosis and necrosis, as indicated by liver histopathological analysis, immunohistochemical analysis, and DNA laddering. Furthermore, according to the results from Western blot analysis, EEP decreased APAP-induced caspase-3 and caspase-8 protein expressions in mouse livers markedly. CONCLUSION: All these results suggest that the protective effects of EEP against APAP-induced liver injury may involve mechanisms associated with its inhibitive effects of lipid peroxidation and the down-regulation of TNF-alpha mediated apoptosis. In a word, EEP could be a valuable candidate for further development for prevention and treatment of hepatic injury.

Protective Effects of the Supernatant of Ethanol Eluate from Artemisia sacrorum Ledeb. against Acetaminophen-Induced Liver Injury in Mice [corrected].

This study was designed to investigate the protective effects of the active part of Artemisia sacrorum Ledeb. Extract (ASE) against acetaminophen (APAP)-induced hepatotoxicity in mice. As a result, pretreated with ASE prior to the administration of APAP significantly prevented the increases of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-alpha (TNF-alpha) levels in serum, and glutathione (GSH) depletion, malondialdehyde (MDA) accumulation in liver tissue. In addition, ASE prevented APAP-induced apoptosis and necrosis, as indicated by a liver histopathological analysis and DNA laddering. Furthermore, according to the results from Western blot analysis, ASE markedly decreased APAP-induced caspase-3 and -8 protein expressions in mouse livers. All these results suggest that the protective effects of ASE against APAP-induced liver injury may involve mechanisms associated with its inhibitive effects of lipid peroxidation and the down-regulation of TNF-alpha mediated apoptosis.

Characteristics and emission factors of PCDD/Fs in various industrial wastes in South Korea.

Since South Korea ratified Stockholm Convention in January 2007, there is an obligation to survey the national emission of PCDD/Fs through environmental routes other than the air for taking actions to reduce and/or eliminate the release of PCDD/Fs. In this study, PCDD/F-containing wastes from various industrial emission sources in Korea (n=388) except from incinerators were investigated to elucidate the emission characteristics and their emission factors of PCDD/Fs in each industry. The concentrations of PCDD/Fs in waste samples ranged ND-96,200 ng I-TEQ kg(-1) (or 66,600 ng WHO-TEQ kg(-1)) for solid phase samples and ND-11,100 pg I-TEQL(-1) (or 6800 ng WHO-TEQ L) for liquid samples, respectively. Elevated levels of PCDD/F concentrations and emission factors were found in the wastes from productions of Cu, Al, Zn, Iron/steel, Pb, EDC/VCM/PVC and from waste landfill sites. The wastes from productions of cement (kilns) and acetylene (carbide method) showed elevated levels of PCDD/F emission factors only. The dominant congeners were OCDD, OCDF, 1,2,3,4,6,7,8-HpCDF and 1,2,3,4,5,7,8-HpCDD. The PCDF ratios in samples from thermal processes and solid phase samples were 69% and 70%, respectively. The ratio of OCDD congener (about 23.5%) was higher than that of other congeners in both solid and liquid phase wastes. These results can be used as a useful reference for the establishment of the PCDD/F inventory and their management plans.

Suppressing effect of goethite on PCDD/F and HCB emissions from plastic materials incineration.

Polyethylene (PE) and polyvinyl chloride (PVC) are the leading plastics in total production in the world. The incineration of plastic-based materials forms many chlorinated compounds, such as polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs). In this study the addition of goethite (alpha-FeOOH) was investigated to determine its suppressing effect on the emission of PCDD/Fs and hexachlorobenzene (HCB) during the combustion of wastes containing PE and PVC. Goethite was being considered since it acts as a dioxin-suppressing catalyst during incineration. Results showed that incorporation of goethite greatly reduced the generation of PCDD/Fs and HCB in the exhaust gas and fly ash. The concentration of PCDD/Fs in flue gas decreased by 45% for lab-scale and 52% for small incinerator combustion experiments, where the goethite ratios in feed samples were 0.54% and 0.34%, respectively. Under the same conditions, the concentration of HCB in flue gas decreased by 88% and 62%, respectively. The present study showed a possible mechanism of the suppressing effect of the goethite for PCDD/F formation. It is likely that iron chlorides react with particulate carbon to form organo-chlorine compounds and promote PCDD/F formation in the gas phase. XRD analysis of combustion ash revealed that the goethite was partially dehydrated and converted to alpha-Fe(2)O(3) and Fe(3)O(4) but no iron chlorides formation. Therefore the goethite impregnated plastics can contribute the reduction of PCDD/Fs and HCB in the exhaust gas during incineration of MSW.

[Studies on chemical constituents from roots of Caragana microphylla].

OBJECTIVE: To study the chemical constituents in roots of Caragana microphylla. METHOD: The constituents were isolated by silica gel column chromatography, and their structures were identified by spectroscopic methods and chemical evidence. RESULT: Eight compounds were identified as beta-sitosterol (1), pseudobaptigenin (2), pentacosanylferulates (3), heptadecanylferulates (4), ferulic acid (5), daucosterol (6), trifolirhizin (7), ononin (8) respectively. CONCLUSION: Compounds 1, 3-7 were obtained from the plant for the first time, and 3, 4, 5 and 7 were obtained from the genus Caragana for the first time.

Assessment of PCDD/F risk after implementation of emission reduction at a MSWI.

Municipal solid waste incinerators (MSWIs) have been shown to be important sources of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). The emission of PCDD/Fs by MSWIs is a controversial subject in human health risk assessment. In this study the effect of a MSWI on a residential area was assessed before and after the installation of an additional treatment system for flue gas. This additional treatment system resulted in a dramatic decrease in PCDD/F concentrations in stack flue gas samples by 99.98%, while the concentrations in air decreased by approximately 50% (36,500 and 0.75 pg I-TEQ m(-3) for air in 1999; 3.5 and 0.38 pg I-TEQ m(-3) in 2002; 1.6 and 0.076 pg I-TEQ m(-3) in 2005 for stack gas and air, respectively). Considering the congener distributions of PCDD/Fs between stack flue gas and air samples, the study area seemed to have been contaminated by other urban sources as well as the MSWI. ISC3 model results support the conclusion that this incinerator became only a minor contributor to the study area after installation of the supplementary systems. This resulted from both proper MSWI operation using modern technology and additional sources of contaminants in this region. Finally, PCDD/F uptake by humans through inhalation of contaminated air was estimated. Assuming that inhalation exposure contributes 10% of total exposure, total exposure was lower than WHO guidelines. These results confirm that proper operation and maintenance of the incinerator led to a reduction in emissions and potential health impacts of PCDD/Fs.

Emission of PCDD/Fs and dioxin-like PCBs from metallurgy industries in S. Korea.

The metallurgy industry and municipal waste incinerators are considered the main sources of polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs) in many countries. This study investigated the emission factors and total emissions of PCDD/Fs and dioxin-like polychlorinated biphenyls (PCBs) emitted from metallurgy industries (including ferrous and nonferrous foundries) in Korea. The toxic equivalency (TEQ) emission factor of PCDD/Fs was the highest for secondary copper production, at 24451 ng I-TEQ/ton. The total estimated emissions of PCDD/Fs from these sources were 35.259 g I-TEQ/yr, comprising 0.088 g I-TEQ/yr from ferrous foundries, 31.713 g I-TEQ/yr from copper production, 1.716 g I-TEQ/yr from lead production, 0.111 g I-TEQ/yr from zinc production, and 1.631 g I-TEQ/yr from aluminum production. The total estimated annual amounts of dioxin-like PCBs emitted from these sources were 13.260 g WHO-TEQ/yr, comprising 0.014 g WHO-TEQ/yr from ferrous foundries, 12.675 g WHO-TEQ/yr from copper production, 0.170 g WHO-TEQ/yr from lead production, 0.017 g WHO-TEQ/yr from zinc production, and 0.384 g WHO-TEQ/yr from aluminum production. The highest emission factor was found for secondary copper smelting, at 9770 ng WHO-TEQ/ton.

4'-O-Alkyaloenin derivatives and their sulfates directed toward overcoming multidrug resistance in tumor cells.

The cytotoxic effects on HCT 116, Hep G2 and HCT 116/VCR 100-1-1 cell lines of synthetic 4'-O-alkylaloenins (2-17), 4'-O-benzylaloenin (18) and 4'-O-allylaloenin (19) were examined by MTT assay, and compared with that of aloenin (1) isolated from Aloe arborescens Mill. Var. natalensis Berger which showed no marked effect (IC50 value: > 100 microM). The cytotoxic effects of 4'-O-alkylaloenin sulfates (21-29) were also examined on the same cell lines. The introduction of a longer alkyl group at the O-4' position of 1 resulted in a higher cytotoxic action on HCT 116 and Hep G2 cells. Among 4'-O-alkylaloenins 2-17, 4'-O-tetradecylaloenin 14 was the most cytotoxic to both on HCT 116 cells (IC50 value: 5.3+/-2.3 microM) and Hep G2 cells (IC50 value: 4.0+/-0.6 microM). Also among 4'-O-alkylaloenin sulfates 21-29, 4'-O-dodecylaloenin sulfate 29 was the most cytotoxic to both on HCT 116 (IC50 value: 4.8+/-0.2 microM) and Hep G2 cells (IC50 value: 4.0+/-0.5 microM). 4'-O-Alkylaloenins 7-14 and 4'-O-alkylaloenin sulfates 24-29 were also cytotoxic to Hep G2 and HCT 116/VCR 100-1-1 cell lines, which overexpress P-glycoprotein, as well as HCT 116 cell lines which scarcely express it.