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1.
Sci Rep ; 9(1): 6763, 2019 May 01.
Article in English | MEDLINE | ID: mdl-31043641

ABSTRACT

The quadrature continuous-wave (QCW) radar has been extensively studied for small vibrational displacement detection such as non-contact sensing of human vital signals. One of the challenges of the QCW radar is the IQ-imbalance and DC-offset estimation by using curve fitting algorithms. Many algorithms have been proposed and have shown that the fitting error increases when the displacement length is small, in which case sufficient data is not provided to the algorithms. This paper presents a quadrature frequency-group (QFG) radar which utilizes a group of frequencies to enhance the fitting performance even with the small displacement. The grouped-frequencies in the QFG radar gives more data than the single-tone of the QCW radar under the same displacement condition. This paper presents the framework and properties of the QFG radar. Some fitting algorithms for the QFG radar are presented and the most adequate algorithm is suggested by simulation and experiments. Simulation and experimental results shows that the QFG radar outperforms the QCW radar. Specifically, it is shown that the fitting accuracy of the QFG radar is up to 100 times better than the QCW radar in the experiment.

2.
J Korean Med Sci ; 34(8): e56, 2019 Mar 04.
Article in English | MEDLINE | ID: mdl-30833880

ABSTRACT

Heart rate (HR) change during sleepy driving has never been investigated. Healthy volunteers who planned to drive a long distance were recruited and monitored with a 24-hour Holter. Six healthy volunteers were enrolled. Their mean driving time was 297.7 ± 111 minutes. Mean duration of sleepy time while driving was 27 ± 24.5 minutes. Driving HR showed a trend for increment as compared to day time mean HR, from 85 ± 5.6 to 89.8 ± 5.6 beats/min (by 7%) (P = 0.093). Mean HR while sleepy driving significantly decreased to 81.5 ± 9.2 beats/min by 9.3% ± 7.4% (P = 0.046). This pilot study for the first time demonstrated that HR decreased while sleepy driving.


Subject(s)
Automobile Driving , Heart Rate/physiology , Adult , Humans , Male , Middle Aged , Pilot Projects , Sleep Deprivation/psychology , Surveys and Questionnaires
3.
Oncol Rep ; 40(1): 545-553, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29750312

ABSTRACT

In the present study, the anticancer activity of 1­[(3S,4R)­2,2­dimethyl­3­oxo­4­(2­piperidonyl)chroman­6­yl]­3­phenylurea (S32) was investigated by testing its effect in vitro on the growth of HeLa cells. First, we showed that the IC50 value of S32 was ~70 µM by using WST­8 assay, and that it significantly inhibited the proliferation and viability of HeLa cells in a dose­dependent manner after 48 h. Morphological changes in apoptotic cells included cellular shrinkage and nuclear condensation. The results of [3H]­thymidine incorporation and flow cytometric analysis indicated that S32 induced inhibition of DNA replication and G2­phase cell cycle arrest. Moreover, S32 induced the levels of reactive oxygen species (ROS) and decreased the mitochondrial membrane potential (MMP) in a time­dependent manner. Using Annexin V­FITC/propidium iodide (PI) dual staining assay, we found that S32 noticeably increased early apoptosis in HeLa cells in a time­dependent manner. The result of western blot analysis showed that the apoptotic induction was associated with an increase in Bax levels and a decrease in Bcl­2 levels, which led to activation of caspase­8, ­9 and ­3. Taken together, our findings demonstrated that S32 induces mitochondrial­mediated apoptosis in HeLa cells and suggest that S32 has potential as an anticancer drug.


Subject(s)
Cell Proliferation/drug effects , Chromans/pharmacology , DNA Replication/drug effects , Neoplasms/drug therapy , Apoptosis/drug effects , Cell Survival/drug effects , Chromans/administration & dosage , G2 Phase/drug effects , HeLa Cells , Humans , Membrane Potential, Mitochondrial/drug effects , Neoplasms/genetics , Neoplasms/pathology , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects
4.
Bioorg Med Chem ; 23(8): 1684-90, 2015 Apr 15.
Article in English | MEDLINE | ID: mdl-25797162

ABSTRACT

A series of chlorophyll a-based chlorins conjugated with pyridyl or quinoxalyl group at different positions were synthesized, characterized and evaluated for their photodynamic effect in vitro. It was found that all the pyridyl and quinoxalyl chlorins showed promising photocytotoxicities but nontoxic without irradiation in HeLa cells, and the substituted types and positions had a significant influence on the photocytotoxicities of the chlorophyll a-based chlorins. All the chlorins with a pyridyl group at the C-D ring end exhibited relatively high photocytotoxicity as compared to those with 3(2)-pyridyl. Among them, compound 12 conjugated with a pyridyl group at its C12 position showed the best photodynamic effect in HeLa cells with an IC50 value of 0.033µM. These facts, associated with the relative high long wavelength absorptions of those chlorins may provide valuable ways to design and prepare promising photosensitizers for application in photodynamic therapy.


Subject(s)
Chlorophyll/chemistry , Chlorophyll/pharmacology , Neoplasms/drug therapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Porphyrins/chemistry , Porphyrins/pharmacology , Chlorophyll/chemical synthesis , Chlorophyll A , HeLa Cells , Humans , Photochemotherapy , Photosensitizing Agents/chemical synthesis , Porphyrins/chemical synthesis , Pyridines/chemical synthesis , Pyridines/chemistry , Pyridines/pharmacology , Quinoxalines/chemical synthesis , Quinoxalines/chemistry , Quinoxalines/pharmacology
5.
Oncol Rep ; 33(3): 1526-32, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25592775

ABSTRACT

2,4,6,8-(3)-Tetranitrophenyl-3,7-diazabicyclo[3.3.1]nonan-9-one (B16), a bispidinone analog, was synthesized to investigate its effects on cell viability, the cell cycle, and apoptotic pathways in HeLa human cervical cancer cells. B16 decreased the percentage of viable cells in WST-8 assays, and morphological changes associated with apoptotic cell death were observed, including cell shrinkage and disruption. Annexin V-FITC/PI dual staining assays showed that B16 significantly increased the early apoptosis of HeLa cells after 24 h of treatment. Moreover, DNA content analysis and [3H]-thymidine incorporation assays showed that B16 induced S-phase cell cycle arrest and inhibited DNA replication after 24 h of treatment. Following treatment with 25 µM of B16, an increase in reactive oxygen species and a decrease in mitochondrial membrane potential were observed by flow cytometry. In addition, the expression levels of caspase cascade and Bcl-2 family proteins determined by western blotting suggested that the induction of apoptosis by B16 was associated with a caspase- and mitochondrial-dependent pathway in HeLa cells. In conclusion, B16 induced early apoptosis and S-phase cell cycle arrest in HeLa cells via a caspase- and mitochondrial­dependent pathway.


Subject(s)
Apoptosis/drug effects , Azabicyclo Compounds/pharmacology , Membrane Potential, Mitochondrial/drug effects , Nitrobenzenes/pharmacology , S Phase Cell Cycle Checkpoints/drug effects , Uterine Cervical Neoplasms/drug therapy , Aza Compounds/chemistry , Aza Compounds/pharmacology , Azabicyclo Compounds/chemical synthesis , Caspases/biosynthesis , Cell Line, Tumor , DNA Replication/drug effects , Female , HeLa Cells , Humans , Nitrobenzenes/chemical synthesis , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Reactive Oxygen Species/metabolism
6.
Int J Oncol ; 44(1): 327-35, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24190603

ABSTRACT

The present study was carried out to investigate the effect of 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-one (bispidinone) analogs on the in vitro growth of human cervical carcinoma (HeLa) cells. A series of 11 bispidinone analogs was synthesized with substituents, e.g., fluoro/methyl/ethyl/isopropyl/thiomethyl/methoxy groups, at various positions. These compounds were synthesized to identify which substituent and position induced the strongest cytotoxic effect in cancer cells. Among these synthetics, analog 9, which contains methoxy groups, had the most significant cytotoxic effect on HeLa cells, and its IC50 value was less than 13 µM. A WST-8 assay also showed that analog 9 inhibited the proliferation of HeLa cells. By using DNA content analysis, we found that analog 9 induced sub-G1 and G1 phase arrest in a time-dependent manner. A [3H]-thymidine incorporation assay suggested that analog 9 inhibited DNA replication in HeLa cells. On performing light microscopy, morphological changes such as cellular shrinkage and disruption, which are apoptotic features, were observed in HeLa cells. Annexin V/propidium iodide double staining and rhodamine-123 staining showed that analog 9 induced apoptosis and disrupted the intracellular mitochondrial membrane potential in HeLa cells. The western blot analysis results suggested that analog 9 induced mitochondria-mediated apoptosis. In addition, we have shown that analog 9 may play a role in the Fas signaling apoptotic pathway.


Subject(s)
Apoptosis/drug effects , Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Mitochondria/drug effects , Uterine Cervical Neoplasms/drug therapy , Annexin A5/metabolism , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cell Proliferation/drug effects , Female , HeLa Cells , Humans , Membrane Potential, Mitochondrial/drug effects , Signal Transduction/drug effects , Uterine Cervical Neoplasms/pathology
7.
Oncol Rep ; 30(4): 1929-35, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23863920

ABSTRACT

Cytochalasin B (CB) is a cell-permeable mycotoxin. It inhibits cytoplasmic division by blocking the formation of contractile microfilaments, it inhibits cell movement and induces nuclear extrusion. In the present study, we investigated the anticancer activity of CB in HeLa human cervical carcinoma cells. CB showed significant cytotoxicity, with an IC50 of 7.9 µM, in a WST-8 assay and significantly inhibited cell proliferation. Furthermore, results from Annexin V-FITC/propidium iodide double-staining indicated that CB induced early apoptosis of HeLa cells in a time-dependent manner. The cells exhibited apoptotic morphology, including cell shrinkage and nuclear condensation. CB induced cell cycle arrest at the S phase. We also observed inhibition of DNA replication in a [3H]-thymidine incorporation assay. Furthermore, CB induced a time-dependent increase in reactive oxygen species and a decrease in mitochondrial membrane potential. Western blot analysis showed an increase in levels of mitochondrial factors Bax and Bcl-2, which was followed by activation of caspase-9 and -3. These results suggested that CB induced apoptosis via a mitochondrial-dependent pathway in HeLa cells.


Subject(s)
Apoptosis/drug effects , Cytochalasin B/pharmacology , Mitochondria/metabolism , Uterine Cervical Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , DNA Replication/drug effects , Female , HeLa Cells , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , Reactive Oxygen Species/metabolism , S Phase Cell Cycle Checkpoints/drug effects , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , bcl-2-Associated X Protein/metabolism
8.
Int J Oncol ; 43(2): 469-76, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23708884

ABSTRACT

In the present study, a biologically active 4-(trifluoromethyl)phenyl piperazin moiety was linked to a 2,2- dimethyl -2H-benzopyran template to generate (3R,4S)-2,2-dimethyl-6-nitro-4-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl) chroman -3-ol (C110g), and the cellular and molecular mechanisms by which C110g exerts cytotoxic effects on the HeLa human cervical cancer cell line were further investigated. C110g suppressed the viability of HeLa cells in both concentration- and time-dependent manner (IC50 of 17 µM) by inducing DNA damage and G1 cell cycle arrest. Characteristic changes in nuclear morphology and Annexin V/PI staining pointed to apoptosis as the mode of cell death. The levels of p53 and p21 were increased in the C110g-treated cells, with a corresponding increase in Bax/Bcl-2 protein ratio. Subsequently, C110g induced the cytoplasmic release of cytochrome c from the mitochondria accompanied by a decreased mitochondrial membrane potential and activation of caspase-3 and -9. These results confirmed that the C110g transduced the apoptotic signal via the mitochondrial pathway. Caspase-8, typically associated with the initiation of the death receptor pathway, was activated, suggesting the extrinsic pathway might also be involved. However, C110g did not result in reactive oxygen species (ROS) generation. Taken together, these findings indicate that the DNA damage-dependent p53-regulated mitochondrial pathway as well as the extrinsic pathway play a crucial role in C110g-induced apoptosis, which provide a better understanding of the molecular mechanisms of trifluoromethyl benzopyrans in cervical cancer.


Subject(s)
Apoptosis/drug effects , Benzopyrans/pharmacology , G1 Phase Cell Cycle Checkpoints/drug effects , Mitochondria/drug effects , Uterine Cervical Neoplasms/drug therapy , Caspase 3/metabolism , Caspase 9/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cytochromes c/metabolism , Enzyme Activation , Female , HeLa Cells , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Reactive Oxygen Species , Tumor Suppressor Protein p53/metabolism , Uterine Cervical Neoplasms/metabolism , bcl-2-Associated X Protein/metabolism
9.
Bioorg Med Chem Lett ; 22(9): 3126-9, 2012 May 01.
Article in English | MEDLINE | ID: mdl-22483395

ABSTRACT

Four new cytochalasin derivatives (1-4), together with cytochalasin B (5), were isolated from the fungus Phoma sp. obtained from the giant jellyfish Nemopilema nomurai. The planar structure and relative stereochemistry were established by analysis of 1D and 2D NMR data. The absolute configuration was defined by the modified Mosher's method. The compounds showed significant cytotoxicity against a small panel of human solid tumor cell lines (A549, SK-OV-3, SK-MEL-2, XF 498, and HCT15) with IC(50) values in the range of 0.5-30 µM. The cytochalasin B (5) showed obvious cytotoxicity with IC(50) of 7.9 µM against HeLa human cervical carcinoma cells.


Subject(s)
Ascomycota/chemistry , Cytochalasins/pharmacology , Scyphozoa/microbiology , Animals , Antineoplastic Agents/chemistry , Cell Death/drug effects , Cell Line, Tumor , Cytochalasins/chemistry , Dose-Response Relationship, Drug , Early Detection of Cancer , Humans , Inhibitory Concentration 50 , Molecular Structure
10.
Int J Oncol ; 39(6): 1609-17, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21833470

ABSTRACT

In the present study, a series of seven synthetic croma-kalim analogues were prepared and evaluated for cytotoxic effect on human cervical carcinoma HeLa cells using WST-8 assay. A preliminary screening of these cromakalim analogues showed that 1-[(3S,4R)-4-(2-ethoxy-4-methyl-1H-pyrrol-1-yl)-3-hydroxy- 2,2-dimethylchroman-6-yl-3-phenylurea (compound 6) had the highest cytotoxic effect (IC50 of 138 µM) and significantly inhibited HeLa cell proliferation after 36 h. In an effort to understand the cytotoxic mechanism of compound 6, we examined its effect on apoptosis and cell cycle distribution. Our results showed that compound 6 induced marked changes in apoptotic morphology and significantly increased early apoptosis of HeLa cells after 48 h by using Annexin V-FITC/PI dual staining assay. This apoptotic induction was associated with an increase in Bax expression, a decrease in Bcl-2 expression, release of cytochrome c and subsequent activation of caspase-9 and -3, which indicated that compound 6 induced apoptosis via caspase- and mitochondria-dependent pathway. By DNA content analysis and [3H]thymidine incorporation assay, compound 6 was found to induce an increase in the number of cells in G1 phase, accompanied by a decrease in the S phase to prevent DNA synthesis after 24 h of treatment. In addition, compound 6 caused significant DNA damage, as detected by the alkaline comet assay. Taken together, the data demonstrate that compound 6 induces apoptosis in HeLa cells through caspase- and mitochondria-dependent pathway and this apoptotic effect is associated with cell cycle arrest and DNA damage. These findings provide further understanding of the molecular mechanisms of compound 6 in cervical cancer.


Subject(s)
Antineoplastic Agents/toxicity , Apoptosis/drug effects , Caspases/metabolism , Cell Cycle Checkpoints/drug effects , Cromakalim/analogs & derivatives , Cromakalim/chemistry , Mitochondria/drug effects , Phenylurea Compounds/toxicity , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cromakalim/toxicity , Cytochromes c/metabolism , DNA Damage/drug effects , DNA Replication/drug effects , Female , HeLa Cells , Humans , Mitochondria/metabolism , Phenylurea Compounds/chemistry , Proto-Oncogene Proteins c-bcl-2/metabolism
11.
Toxicol In Vitro ; 25(8): 1535-41, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21621599

ABSTRACT

The compound 3,4,5-trihydroxy-N-[2-p-tolylethyl]-benzamide (THTEB) is one of the derivatives of tyrosol, which is p-tyrosol combined with gallic acid by an amide bond. In this study, THTEB displayed a significant antiproliferative effect on human cervical carcinoma (HeLa) cells. Cell cycle analysis revealed that THTEB could arrest HeLa cells in the S phase with a concomitant decrease in the cells' G0/G1 and G2/M phases. According to the [3H]thymidine incorporation assay results, we found that THTEB could inhibit DNA replication, which suggests that THTEB-induced S phase arrest might be the direct result of blocked DNA synthesis. However, THTEB had very weak effect on replication protein A (RPA)'s ssDNA binding activity and the topoisomerase I (topo I)-mediated DNA relaxation activity, signifying that RPA and topo I were not the main target molecules in the inhibition of DNA replication. Furthermore, by using alkaline single-cell gel electrophoresis (comet assay), we found severe DNA damage caused by THTEB. In conclusion, these results suggest that THTEB could induce tumor cell antiproliferation correlated with DNA damage and DNA replication inhibition, but the target molecule of THTEB remains elusive.


Subject(s)
Antineoplastic Agents/toxicity , Benzamides/toxicity , DNA Damage , DNA Replication/drug effects , DNA, Neoplasm/drug effects , Benzamides/chemical synthesis , Cell Proliferation/drug effects , DNA Topoisomerases, Type I/metabolism , DNA, Neoplasm/metabolism , Gallic Acid/analogs & derivatives , Gallic Acid/chemistry , Gallic Acid/toxicity , HeLa Cells , Humans , Phenylethyl Alcohol/analogs & derivatives , Phenylethyl Alcohol/chemistry , Phenylethyl Alcohol/toxicity , Replication Protein A/metabolism , S Phase/drug effects
12.
Oncol Rep ; 24(3): 771-7, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20664986

ABSTRACT

The current study was undertaken to investigate the effects of methyl 5-chloro-4,5-didehydrojasmonate (J7), an analogue of methyl jasmonate, on the in vitro growth of human cervical carcinoma HeLa cells. Significantly decreased rates of viability (IC50 approximately 15 microM) as well as evidence of apoptosis were observed with J7. Cell morphological changes observed under light microscopy confirmed apoptosis occurrence. Furthermore, the results from Annexin V-FITC/PI double staining and the cell cycle arrest assay indicated that J7 induced earlier apoptosis of HeLa cells. J7 also reduced the expression of Bcl-2 and subsequent activation of a protease cascade involving caspase-9 and -3 by Western blot assay was observed. We also found that J7 was able to induce DNA damage. These findings suggest that J7 induces HeLa cell apoptosis by activation of caspase pathway and the apoptotic effect is associated with DNA damage. Therefore, J7 may be a candidate compound to be developed into an anticancer agent.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cyclopentanes/pharmacology , DNA Damage , Fatty Acids, Unsaturated/pharmacology , Caspase 3/metabolism , Caspase 9/metabolism , Cell Cycle/drug effects , Cell Proliferation/drug effects , Cell Shape/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , HeLa Cells , Humans , Inhibitory Concentration 50 , Proto-Oncogene Proteins c-bcl-2/metabolism
13.
Arch Pharm Res ; 33(2): 231-5, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20195823

ABSTRACT

As part of an ongoing search for bioactive metabolites from the fungus Aspergillus versicolor derived from a marine sponge Petrosia sp., an aromatic polyketide derivative (1), two xanthones (2 and 3), and five anthraquinones (4-8) were isolated by bioactivity-guided fractionation. The gross structures were determined based on the NMR and MS spectroscopic data, and the absolute configurations were defined by comparison of optical rotation data with those of reported. Compounds 2, 4, 5, and 7 exhibited significant cytotoxicity against five human solid tumor cell lines (A-549, SK-OV-3, SK-MEL-2, XF-498, and HCT-15) with IC50 values in the range of 0.41-4.61 microg/mL. Compounds 4 and 7 exhibited antibacterial activity against several clinically isolated Gram-positive strains with MIC values of 0.78-6.25 microg/mL.


Subject(s)
Anthraquinones/pharmacology , Aspergillus/metabolism , Macrolides/pharmacology , Petrosia , Xanthones/pharmacology , Animals , Anthraquinones/chemistry , Anthraquinones/isolation & purification , Anti-Bacterial Agents , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cells, Cultured , Drug Screening Assays, Antitumor , Humans , Macrolides/chemistry , Macrolides/isolation & purification , Microbial Sensitivity Tests , Molecular Structure , Xanthones/chemistry , Xanthones/isolation & purification
14.
Biochem Biophys Res Commun ; 385(4): 612-7, 2009 Aug 07.
Article in English | MEDLINE | ID: mdl-19486883

ABSTRACT

Heat shock factor 1 (HSF1) primarily regulates various cellular stress responses. The role of alpha-helix1 (H1) in its DNA-binding domain (DBD) during HSF1 activation remains unknown. Here, HSF1 lacking H1 loses its heat-induced activity, suggesting the importance of the latter. Furthermore, the CD spectra and AMBER prediction show that this H1 deficiency does not change the structure of HSF1 monomer, but does impact its heat-induced trimerization. Point mutation showed that Phe18 in H1 interacts with Tyr60, and that Trp23 interacts with Phe104 by an aromatic-aromatic interaction. Thus, the presence of H1 stabilizes the DBD structure, which facilitates the heat-induced trimerization and DNA-binding of HSF1.


Subject(s)
DNA-Binding Proteins/metabolism , DNA/metabolism , Heat-Shock Response , Transcription Factors/metabolism , Amino Acid Sequence , Binding Sites , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , Heat Shock Transcription Factors , Hot Temperature , Humans , Molecular Sequence Data , Point Mutation , Protein Binding , Protein Multimerization , Protein Stability , Protein Structure, Secondary/genetics , Protein Structure, Tertiary/genetics , Sequence Deletion , Transcription Factors/chemistry , Transcription Factors/genetics
15.
Environ Monit Assess ; 150(1-4): 397-404, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18379891

ABSTRACT

Serum vitellogenin (VTG) contents of wild goldfish (Carassius auratus) were investigated as a sensitive biomarker for artificial estrogenic compounds in aquatic environments. Goldfish was sampled from a pristine area, a river situated 5 km downstream from a sewage treatment works (STW), and also from the Young-San River in Korea. The female yolk precursor protein VTG was not detected when gonadosomatic index (GSI) was less than 0.85%, while VTG levels of >10 microg/ml were found in males whose GSI was less than 1.53%. In male goldfish sampled from STW and the Young-San River, the higher VTG corresponded to lower GSI. This study suggested a trend that gonad development was connected to VTG levels in both sexes, and the application of GSI and histological analysis provide an attractive possibility that it could be included in the panel of markers used for estrogenic activity investigation of aquatic environments.


Subject(s)
Endocrine Disruptors/pharmacology , Estrogens/pharmacology , Goldfish , Gonads , Vitellogenins/blood , Animals , Biomarkers/blood , Environmental Monitoring , Female , Goldfish/anatomy & histology , Goldfish/physiology , Gonads/anatomy & histology , Gonads/drug effects , Gonads/physiology , Humans , Male , Rivers/chemistry , Seasons , Water Pollutants, Chemical/pharmacology
16.
Int J Oncol ; 33(6): 1291-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19020763

ABSTRACT

The apoptogenic and DNA damaging effects of (E)-10-oxooctadec-8-enoic acid (S5C) and (E)-9-oxooctadec-10-enoic acid (S6C), two structurally related fatty acids isolated from Red Alga Gracilaria verrucosa, were compared and their apoptosis-inducing properties characterized against human lung carcinoma (A549) cells. Significantly, the two acids decreased the rates of proliferation and viability (IC50 of approximately 170 and approximately 140 microM) as well as evidence of the induction of apoptosis. Cell morphological changes observed under light microscopy confirmed apoptosis occurrence. The results from Annexin V/PI dual staining and the cell cycle arrest assay indicated that S5C and S6C induced an earlier apoptosis of A549 cells in a concentration-dependent manner. We found that they induced DNA damage and inhibited DNA replication followed by S-phase arrest. In addition, the very sensitive alkaline micro-gel electrophoresis technique (comet assay) was used to estimate the compound-induced DNA single- and double-strand breaks. These findings suggest that S5C and S6C induced A549 cell apoptosis and their effects are associated with DNA damage. Therefore, S5C and S6C have the potential to be developed into anticancer agents due to their relatively easy synthesis and structural manipulation.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , DNA Replication/drug effects , Fatty Acids/pharmacology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Shape/drug effects , Cell Survival/drug effects , DNA Breaks, Double-Stranded , DNA Breaks, Single-Stranded , Dose-Response Relationship, Drug , Humans , Inhibitory Concentration 50 , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Time Factors
17.
Biochemistry ; 47(22): 6007-15, 2008 Jun 03.
Article in English | MEDLINE | ID: mdl-18457423

ABSTRACT

Under circumstances of heat stress, heat shock transcription factor 1 (HSF1) plays important roles in heat shock protein expression. In this study, an increasing concentration of dithiothreitol (DTT) was found to either enhance or inhibit the heat-induced trimerization of HSF1, suggesting the involvement of dual redox-dependent HSF1 activation mechanisms. Our in vitro experiments show that the heat-induced bonding between the cysteine C36 and C103 residues of HSF1 forms an intermolecular disulfide covalent bond (SS-I bond) and that it directly causes HSF1 to trimerize and bond to DNA. Gel filtration assays show that HSF1 can form intermolecular hydrophobic interaction-mediated (iHI-m) noncovalent oligomers. However, the lack of a trimerization domain prevents HSF1 activation, which suggests that iHI-m noncovalent trimerization is a precondition of SS-I bond formation. On the other hand, intramolecular SS-II bond (in which the C153, C373, and C378 residues of HSF1 participate) formation inhibits this iHI-m trimerization, thereby preventing SS-I bond formation and DNA binding. Thus, HSF1 activation is regulated positively by intermolecular SS-I bond formation and negatively by intramolecular SS-II bond formation. Importantly, these two SS bonds confer different DTT sensitivities (the SS-II bond is more sensitive). Therefore, a low concentration of DTT cleaves the SS-II bond but not the SS-I bond and thus improves DNA binding of HSF1, whereas a high concentration DTT cuts both SS bonds and inhibits HSF1 activation. We propose that these interesting effects further explain cellular HSF1 trimerization, DNA binding, and transcription when cells are under stress.


Subject(s)
DNA-Binding Proteins/chemistry , DNA-Binding Proteins/metabolism , DNA/metabolism , Transcription Factors/chemistry , Transcription Factors/metabolism , Binding Sites , Cysteine/genetics , Cysteine/metabolism , Dithiothreitol , Heat Shock Transcription Factors , Humans , Models, Biological , Oxidation-Reduction
18.
J Nat Prod ; 71(2): 232-40, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18220352

ABSTRACT

A chemical study on the anti-inflammatory components of the red alga Gracilaria verrucosa led to the isolation of new 11-deoxyprostaglandins ( 1- 4), a ceramide ( 5), and a C 16 keto fatty acid ( 6), along with known oxygenated fatty acids ( 7- 14). Their structures were elucidated on the basis of NMR and MS data. The absolute configurations of compounds 1- 5 were determined by Mosher's method. The anti-inflammatory activity of the isolated compounds ( 1- 14) was evaluated by determining their inhibitory effects on the production of pro-inflammatory mediators (NO, IL-6, and TNF-alpha) in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells. Compounds 9 and 10 exhibited the most potent activity. In the evaluation of these two compounds and derivatized analogues ( 15- 40), the anti-inflammatory activity was enhanced in some synthetic analogues. These enone fatty acids were investigated as potential anti-inflammatory leads for the first time.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Gracilaria/chemistry , Macrophages/metabolism , Prostaglandins E/isolation & purification , Prostaglandins E/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Fatty Acids/chemical synthesis , Fatty Acids/chemistry , Fatty Acids/isolation & purification , Fatty Acids/pharmacology , Inflammation/chemically induced , Inflammation/drug therapy , Interleukin-6/biosynthesis , Korea , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/analysis , Nitric Oxide/biosynthesis , Prostaglandins E/chemical synthesis , Prostaglandins E/chemistry , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/biosynthesis
19.
Oncol Rep ; 19(2): 535-9, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18202804

ABSTRACT

The polyamines are aliphatic cations which are present in millimolar concentrations in all mammalian cells, and are required for optimal growth of almost all cell types. In this study, the roles of polyamines in DNA replication in vitro and the mechanism by which polyamines affected DNA replication were examined using simian virus 40 DNA replication system in vitro. We found that polyamines inhibited DNA replication, but it is not clear at which stage this occurs. Spermidine inhibited the DNA cleavage by topoisomerase I at 8.0 mM, but stimulated its activity at 1.0 mM. Spermine also inhibited its activity at 4.0 mM, but stimulated at 1.0 mM. The ssDNA binding activity of replication protein A was slightly affected by polyamines. Polyamines, especially spermine, also significantly reduced polymerase alpha-primase activity at 133 microM. Taken together, we suggest that the major inhibition of SV40 DNA replication may be due to the inhibition of pol alpha-primase activity, and possible roles for polyamines in the initiation process are discussed.


Subject(s)
DNA Polymerase I/antagonists & inhibitors , DNA Primase/antagonists & inhibitors , DNA Replication , Spermidine/physiology , Spermine/physiology , DNA Cleavage/drug effects , DNA Replication/drug effects , DNA, Single-Stranded/drug effects , DNA, Single-Stranded/metabolism , Humans , Polyamines/pharmacology , Replication Protein A/antagonists & inhibitors , Simian virus 40/drug effects , Simian virus 40/genetics , Spermidine/pharmacology , Spermine/pharmacology , Topoisomerase I Inhibitors
20.
Oncol Rep ; 19(2): 527-34, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18202803

ABSTRACT

p-Tyrosol is a phenolic compound present in different dietary sources that can exert mild antioxidant properties based on in vitro and in vivo studies. In our study, two p-tyrosol derivatives (p-tyrosyl gallate and p-tyrosyl acetate) were synthesized and compared together with p-tyrosol and gallic acid for their cytotoxic activities on human cancer cells. p-Tyrosyl gallate had the most potent cytotoxicity and the major cytotoxic mechanism of its action was studied. We found that in HeLa cells, p-tyrosyl gallate can effectively induce cell cycle arrest during S phase and inhibited in vitro simian virus (SV40 DNA) replication. In addition, p-tyrosyl gallate can inhibit three important functional replication proteins (topoisomerase I, RPA and pol alpha-primase), especially pol alpha-primase. These results suggest that p-tyrosyl gallate-induced cell cycle arrest during S phase correlates with the inhibition of DNA replication. Pol alpha-primase may be the main target molecule. Taken together, we suggest that p-tyrosyl gallate is a strong anticancer drug candidate that warrants further investigation.


Subject(s)
Antineoplastic Agents/pharmacology , DNA Polymerase I/antagonists & inhibitors , DNA Primase/antagonists & inhibitors , DNA Replication/drug effects , Enzyme Inhibitors/pharmacology , Phenylethyl Alcohol/analogs & derivatives , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Cycle/drug effects , DNA, Single-Stranded/drug effects , DNA, Single-Stranded/metabolism , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , HeLa Cells , Humans , Phenylethyl Alcohol/chemical synthesis , Phenylethyl Alcohol/chemistry , Phenylethyl Alcohol/pharmacology , Simian virus 40/drug effects
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