• Korean Journal of Medicinal Crop Science
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• v.12 no.4
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• pp.304-308
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• 2004

Immune enhancing activities of water and ethanol extracts of Hypericum perforatum L. (HP) were examined. HP extracts inhibited the growth of human hepatocarcinoma, human gastric cancer cell and human breast cancer cells in concentration-dependent mammers over a concentration range of $0.05{\sim}1.0\;mg/ml$, showing inhibiton of more than 80% with the concentration of 1.0 mg/ml. However, HP the same concentration. Overall selectivity of the extracts on the three human cancer lines was over 3.5, which is higher than those from the conventional herbs. The growth of human immune B and T cells was enhanced up to 1.4 to 2.0 folds by the addition of the extracts for 4 days, compared to controls. Ethanol extracts of HP after 6 days incubation increased the secretions of tumor necrosis factor-alpha $(TNF-{\alpha})$ from T cells and interleukin-6 (IL-6) from B cells to 6.7 pg/cell and 6.8 pg/cell, respectively. These results suggest that HP has a potent immune enhancing effect.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4969-4976
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• 2014

Background: miR-152 is involved in the genesis and development of several malignancies. However, its role in HCC has not been fully clarified. The aim of this study was to investigate the clinicopathological significance of miR-152 and its effect on the malignant phenotype of HCC cells. Methods: miR-152 expression was detected using real-time quantitative RT-PCR in 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissues. Functionally, in vitro effects and mechanisms of action of miR-152 on proliferation, viability, caspase activity, apoptosis and motility were explored in HepG2, HepB3 and SNU449 cells, as assessed by spectrophotometry, fluorimetry, fluorescence microscopy, wound-healing and Western blotting, respectively. Results: miR-152 expression in HCC was downregulated remarkably compared to that in adjacent hepatic tissues. miR-152 levels in groups of advanced clinical stage, larger tumor size and positive HBV infection, were significantly lower than in other groups. A miR-152 mimic could suppress cell growth, inhibit cell motility and increase caspase activity and apoptosis in HCC cell lines. Furthermore, Western blotting showed that the miR-152 mimic downregulated Wnt-1, DNMT1, ERK1/2, AKT and TNFRS6B signaling. Intriguingly, inverse correlation of TNFRF6B and miR-152 expression was found in HCC and bioinformatics confirmed that TNFRF6B might be a target of miR-152. Conclusions: Underexpression of miR-152 plays a vital role in hepatocarcinogenesis and lack of miR-152 is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis. miR-152 may act as a tumor suppressor miRNA by also targeting TNFRSF6B and is therefore a potential candidate biomarker for HCC diagnosis, prognosis and molecular therapy.

• Molecules and Cells
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• v.37 no.12
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• pp.873-880
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• 2014

In our previous study, miRNA-183, a miRNA in the miR-96-182-183 cluster, was significantly over-expressed in esophageal squamous cell carcinoma (ESCC). In the present study, we explored the oncogenic roles of miR-183 in ESCC by gain and loss of function analysis in an esophageal cancer cell line (EC9706). Genome-wide mRNA micro-array was applied to determine the genes that were regulated directly or indirectly by miR-183. 3'UTR luciferase reporter assay, RT-PCR, and Western blot were conducted to verify the target gene of miR-183. Cell culture results showed that miR-183 inhibited apoptosis (p < 0.05), enhanced cell proliferation (p < 0.05), and accelerated G1/S transition (p < 0.05). Moreover, the inhibitory effect of miR-183 on apoptosis was rescued when miR-183 was suppressed via miR-183 inhibitor (p < 0.05). Western blot analysis showed that the expression of programmed cell death 4 (PDCD4), which was predicted as the target gene of miR-183 by microarray profiling and bioinformatics predictions, decreased when miR-183 was over-expressed. The 3'UTR luciferase reporter assay confirmed that miR-183 directly regulated PDCD4 by binding to sequences in the 3'UTR of PDCD4. Pearson correlation analysis further confirmed the significant negative correlation between miR-183 and PDCD4 in both cell lines and in ESCC patients. Our data suggest that miR-183 might play an oncogenic role in ESCC by regulating PDCD4 expression.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.487-493
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• 2018

Cluster of differentiation 44 (CD44), a cell surface receptor for hyaluronic acid (HA), is involved in aggressive cancer phenotypes. Herein, we investigated the role of the CD44 standard isoform (CD44s) in hypoxia-inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) regulation using MCF7 overexpressing CD44s (pCD44s-MCF7). When pCD44s-MCF7 was incubated under hypoxia, levels of $HIF-1{\alpha}$, vascular endothelial growth factor, and the $HIF-1{\alpha}$ response element-derived luciferase activity were significantly increased compared to those in the control MCF7. Incubation of pCD44s-MCF7 cells with HA further increased $HIF-1{\alpha}$ accumulation, and the silencing of CD44s attenuated $HIF-1{\alpha}$ elevation, which verifies the role of CD44s in $HIF-1{\alpha}$ regulation. In addition, the levels of phosphorylated extracellular signal-regulated kinase (ERK) was higher in hypoxic pCD44s-MCF7 cells, and $HIF-1{\alpha}$ accumulation was diminished by the pharmacological inhibitors of ERK. CD44s-mediated $HIF-1{\alpha}$ augmentation resulted in two functional outcomes. First, pCD44s-MCF7 cells showed facilitated cell motility under hypoxia via the upregulation of proteins associated with epithelial-mesenchymal transition, such as SNAIL1 and ZEB1. Second, pCD44s-MCF7 cells exhibited higher levels of glycolytic proteins, such as glucose transporter-1, and produced higher levels of lactate under hypoxa. As a consequence of the enhanced glycolytic adaptation to hypoxia, pCD44s-MCF7 cells exhibited a higher rate of cell survival under hypoxia than that of the control MCF7, and glucose deprivation abolished these differential responses of the two cell lines. Taken together, these results suggest that CD44s activates hypoxia-inducible $HIF-1{\alpha}$ signaling via ERK pathway, and the $CD44s-ERK-HIF-1{\alpha}$ pathway is involved in facilitated cancer cell viability and motility under hypoxic conditions.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.2
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• pp.217-222
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• 2003

We studied effects of hot water extract of Lentinus edodes (Berk.)sing. and Pleurotus eryngii (De Candolle ex Fries) Quel mushroom on proliferation and apoptosis of the human colon adenocarcinoma, HT-29 and Caco-2.. Cells were maintained with Dulbecco's modified Eagle medium/Ham's F-12 nutrient mixture supplemented with 10% fetal bovine serum at 37$^{\circ}C$ in a humidified $CO_2$. For cell proliferation experiments, cells were seeded in 35 mm dishes, treated with the various concentrations of the extract for the different time course. Apoptosis was measured by caspase-3 activity The more contents of the extract added in HT-29 and Caco-2 were, the more cell proliferation was suppressed. When we incubated HT-29 cells for 24, B\ulcorner72, and 96 hours after treatments, cell proliferation was markedly suppressed after 96 hours. Also, caspase-3 activity in HT-29 was increased by the treatment of Lentinus edodes and Pleurotus eryngii extracts. However, the treatment of the extract to SNU484, Korean stomach adenocarcinoma, did not show any influence on cell proliferation and caspase-3 activity Therefore, Lentinus edodes and Pleurotus eryngii are strongly recommended for the prevention and treatment of colon cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.5
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• pp.922-934
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• 2000

To investigate the composition of carotenoids present in marine organisms and the biological activity of the carotenoids, carotenoids of the muscles and tunic of tunicates and shellfishes were isolated and identified. Anitmutagenic activities of the carotenoids for S. typhimurium TA 98 and cytotoxic activity for cancer cell lines were determined. Total carotenoid contents in the muscle of tunicata ranged from 18.65 mg% to 2.39 mg%. The highest amount of the total carotenoid was found in the muscle of Halocynthia aurantium, followed by Styela clava (HERDMAN), H. roretzi, H. hilgendorfi f. igaboya, H. hilgendorfi f. retteri, S. plicata (LESUEUR) in order. Interestingly, total carotenoid content in the muscle of S. clava (HERDAMAN) was higher than that of H. roretzi. Total carotenoid content of all tunicata, other than H. aurantium and H. roretzi, were higher in muscle than tunic. The major carotenoids in H. roretzi, H. aurantium, S. plicata (LESUEUR), and S. clava (HERDAMAN) were cynthiaxanthin (25.1∼42.2%), halocynthiaxanthin (9.7∼26.3%), diatoxanthin (8.0∼18.7%) and β-carotene (7.7%∼21.7%). Similarly, cantaxanthin (19.6%), cynthiaxanthin (15.4%), halocynthiaxanthin (14.8%), and (3R, 3'R), (3S, 3'S)-astaxanthin (22.6%) in H. hilgendorfi f. retteri and fucoxanthin (26.6%), cynthiaxanthin (21.8%), halocynthiaxanthin (15.2%), and β-carotene (9.3%) in H. hilgendorfi f. igaboya were major carotenoids in both tunicate. However, the composition of carotenoids in muscle and tunic of tunicata was similar each other. Among the shellfishes examined, total carotenoid content of the muscle of Peronidia venulosa (Schrenck) and Corbicula fluminea, and of the gonad of Atrina pinnata and Chlamys farreri, was ranged from 2.51 to 6.83 mg% which were relatively higher than that of other shellfishes. The composition of the carotenoids of shellfishes, which might depend upon their living environments, was varied. But cynthiaxanthin (15.9∼39.0%) and zeaxanthin (9.6∼21.9%) in gonad of C. farreri, and muscles of Buccinum Volutharpa perryi (JAY) and Crassostrea gigas, cynthiaxanthin (21.5∼48.6%) and mytiloxanthin (14.6%) in muscle of C.fluminea and gonad of A. pinnata, and canthaxanthin (60.6%) and isozeaxanthin (20.5%) in muscles of P. venulosa (Schrenck), and β-carotene (23.7%∼37.8%) and zeaxanthin (18.2∼20.4) in muscles of Semisulcospira libertina and Meretrix lusoria were major carotenoids. Interestingly, diester type-carotenoids were present along with free type-carotenoids in muscles of C. gigas. antimutagenic effect of the carotenoids isolated from tunicata and shellfishes against 2-amino-3-methylimidazol [4,5-f]quinoline (IQ) for S. typhimurium TA 98 was proportional to the amount (20, 50 and 100㎍/plate) treated. Mutagenicity of IQ was significantly reduced by astaxanthin, isozeaxanthin, mytiloxanthin and halocynthiaxanthin, whereas the mutagenicity of aflatoxin B₁(AFB₁) was significantly reduced by β-carotene, isozeaxanthin, and mytiloxnthin. Growth inhibition effect of carotenoids isolated from tunicata and shellfishes for cancer cell was proportional to the amount (5, 10, and 20㎍/plate) treated. The growth of HeLa cell by β-carotene, cynthiaxanthin, astaxanthin and halocynthiaxanthin, NCI-H87 cell by β-carotene, astaxanthin, cynthiaxanthin, and halocynthiaxanthin, HT-29 cell by β-carotene, cynthiaxanthin, mytiloxanthin and halocynthiaxanthin, and MG-63 cells by β-carotene, cynthiaxanthin, astaxanthin, canthaxanthin and halocynthiaxanthin were statistically reduced.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.7
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• pp.826-833
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• 2008

The effects of porphyran-chungkookjang on cytotoxicity of human normal cell line (BJ) and human cancer cell lines (AGS and HT-29) were examined. Porphyran, which was prepared from laver (Porphyra yezoensis), decreased the viability of the cancer cells, however, it did not affect the viability of normal cells. Porphyranchungkookjang was prepared by the addition of 5% (w/w) porphyran into chungkookjang which was fermented by starter, Bacillus subtilis DJI. The cytotoxicity effects of the chungkookjang and porphyran-chungkookjang were evaluated with MTT assay. The methanol and the water extract of porphyran-chungkookjang at 1.0 mg/mL showed $23{\sim}38%$ decreases in proliferation of cancer cells (AGS and HT-29). However, the methanol and the water extracts of porphyran-chungkookjang did not inhibit the growth of normal cell. Moreover, the methanol extract of porphryan-chungkookjang at 1.0 mg/mL showed $1.2{\sim}1.5$ fold higher anticancer effects than that of the chungkookjang.

• Journal of Life Science
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• v.13 no.3
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• pp.314-323
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• 2003

The purpose of this study was to examine the effects of xenobiotic nuclear receptors, CAR, SXR, and PPAR${\gamma}$ on the transcriptional activity of estrogen receptor in human breast cancer cell lines and compare with those in human hepatoma cell line. Two different breast cancer cell lines, MCF-7 and MDA-MB-231 were cultured and effects of CAR, SXR, and PPAR${\gamma}$ on the ER-mediated transcriptional activation of synthetic (4ERE)-tk-luciferase reporter gene were analyzed. Consistent with the previous report, CAR significantly inhibited ER-mediated transactivation and SXR repressed modestly whereas the PPAR${\gamma}$ did not repress the ER-mediated transactivation. However, in breast cancer cells neither of the xenobiotic receptors repressed the ER-mediated transactivation. Instead, they tend to increase the transactivation depending on the cell type and xenobiotic nuclear receptors. In MCF-7, SXR but neither CAR nor PPAR${\gamma}$ slightly increased ER-mediated transactivation whereas in MDA-MB-231, CAR and PPAR${\gamma}$ but not SXR tend to increase the transactivation of the reporter gene. These results indicate that the effects of ER cross-talk by the CAR, SXR, and PPAR${\gamma}$ , are different in breast cancer cells from hepatoma cells. In conclusion, the transcriptional regulation by estrogen can involve different cross-talk interaction between estrogen receptor and xenobiotic nuclear receptors depending on the estrogen target cells.

• Carbon letters
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• v.17 no.1
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• pp.45-52
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• 2016

The attachment of 2-aminobenzamide to carboxylated multi-wall carbon nanotubes (MWCNTs)-COOH was achieved through the formation of amide bonds. Then, the functionalized MWCNTs, MWCNT-amide, were treated by phosphoryl chloride to produce MWCNT-quin. The products were characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, thermogravimetric analysis, derivative thermogravimetric, steady-state fluorescence spectroscopy, and solubility testing. MWCNT-quin showed photo-electronic properties, which is due to the attachment of the 4-hydroxyquinazoline groups to them as proved by steady-state fluorescence spectroscopy. This suggests intramolecular interactions between the tubes and the attached 4-hydroxyquinazoline. The toxicity of the samples was evaluated in human embryonic kidney HEK293 and human breast cancer SKBR3 cell lines, and the viable cell numbers were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) after the cells were cultured for 24 h. Cellular investigations showed that the modified MWCNTs, particularly MWCNT-quin, have considerably significant toxic impact on SKBR3 as compared to HEK293 at the concentration of 5 µg/mL.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.14-22
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• 2009

In vitro cytotoxicity of 23 alkyl phenols (APs) on human cervical cancer cell lines (HeLa) was determined using the lactate dehydrogenase (LDH) cytotoxicity assay. Two different sets of descriptors were used to construct the calibration model based on Genetic Algorithm-Multiple Linear Regression (GA-MLR) based on the experimental data. A statistically robust Structure-Activity Relationships (QSAR) model was achieved ($R^2$=95.05%, $Q^2_{LOO}$=91.23%, F=72.02 and SE= 0.046) using three Dragon descriptors based on Me (0D-Constitutional descriptor), BELp8 (2D-Burden eigenvalue descriptor) and HATS8p (3D-GETAWAY descriptor). However, external validation could not fully prove its validity of the selected QSAR in characterization of the cytotoxicity of APs towards HeLa cells. Nevertheless, the cytotoxicity profiles showed a finding that 4-n-octylphenol (4-NOP), 4-tert-octyl-phenol (4-TOP), 4-n-nonylphenol (4-NNP) had a more potent cytotoxic effect than other APs tested, inferring that increased length and molecular bulkiness of the substituent had important influence on the LDH cytotoxicity.