• Radiation Oncology Journal
• /
• v.34 no.3
• /
• pp.230-238
• /
• 2016

Purpose: Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Materials and Methods: Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Results: Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. Conclusion: In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

• Journal of Ginseng Research
• /
• v.40 no.3
• /
• pp.304-308
• /
• 2016

Background: Joboksansam, Korean bird wild ginseng, is an artificially cultivated wild ginseng germinated from bird feces. Although numerous pharmacologic activities of wild ginsengs have been reported, the beneficial effect of joboksansam in cancer has not been elucidated. In this study, we investigated the in vivo and in vitro anticancer activities of joboksansam powder. Methods: To evaluate the in vivo anticancer activity of joboksansam, we established a xenograft mouse model bearing RMA cell-derived cancer. Direct cytotoxicity induced by joboksansam powder was also investigated in vitro using (3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) assay. The inhibitory activity of this powder on the activation of cell survival signaling involving Akt and Src was examined with immunoblot analysis. Results: Joboksansam powder displayed strong inhibitory activity against the increased tumor size, increased weight of total body and cancer tissues, and mortality of tumor-bearing mice. Joboksansam powder also suppressed the activation of survival regulatory enzymes Akt and Src, as assessed by phosphorylation levels in the immunoblot analysis of tumor tissues. Interestingly, the viability of RMA cells in vitro was directly decreased by joboksansam treatment. Conclusion: Overall, our results strongly suggest that joboksansam powder has the potential to protect against cancer generation by direct cytotoxic effects on cancer cells resulting from suppression of cell survival signaling.

• YAKHAK HOEJI
• /
• v.35 no.3
• /
• pp.203-215
• /
• 1991

Using the calorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT)assay, we evaluated the chemosensitivity of 8 anticancer drugs{vincristine(VCR), vinblastine(VBL), adriamycin(ADR), cisplatin(CPDD), etoposide(VP-16), cytosine arabinoside(ara-C), bleomycin (Bleo) and cyclophosphamide(CYC)} and the cytotoxicity-enhancing effects of ($\pm$)-ar-turmerone and the extracts of the crude drugs {Lithospermum eythrorhizon(LE) and Scutellaria baicalensis (SB)} on the above mentioned anticancer drugs against HL-60 and KG-1 cells among 8 anticancer drugs, VCR, VBL, ADR, and CPDD inhibited the growth of both cell lines by more than 50%, while VP-16, ara-C, Bleo, and CYC were less effective. ($\pm$)-ar-Turmerone had significant inhibitory effects against both cell lines, showing the ID$_{50}$ values of 11.730 $\mu\textrm{g}$/ml and 0.292 $\mu\textrm{g}$/ml for HL-60 and KG-1 cells. respectively. But the extracts of LE and SB roots showed no significant cytotoxic effects. According to ID$_{50}$ values, the cytotoxicities of VCR, VBL and ADR against HL-60 were enhanced two, eight and three times by mixing ($\pm$)-ar-turmerone, five, seven and three times by adding the extract of LE root, and twenty, six and three times by mixing the extract of SB root, respectively. The cytotoxicities of the above mentioned drugs against KG-1 cell were enhanced two, seven and three times by mixing ($\pm$)-ar-turmerone, two, three and three times by combining wilth the extract of LB root, and two, five and two times by adding the extract of SB root, respectively. The cytotoxicity-potentiating effects of ($\pm$)-ar-turmerone and the extracts of LE and SB roots against HL-60 cell were greater than KG-1 cell.

• Journal of Ginseng Research
• /
• v.43 no.1
• /
• pp.95-104
• /
• 2019

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.1
• /
• pp.205-209
• /
• 2012

Background: The inhibition of tumor cell growth without toxicity to normal cells is an important target in cancer therapy. One possible way to increase the efficacy of anticancer drugs and to decrease toxicity or side effects is to develop traditional natural products, especially from medicinal plants. Paris polyphylla Smith has shown anti-tumour effects by inhibition of tumor promotion and inducement of tumor cell apoptosis, but mechanisms are still not well understood. The present study was to explore the effect of Paris polyphylla Smith extract (PPSE) on connexin26 and growth control in human esophageal cancer ECA109 cells. Methods: The effects of PPSE on Connexin26 were examined by RT-PCR, western blot and immunofluorescence; cell growth and proliferation were examined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Results: PPSE inhibited the growth and proliferation on esophageal cancer ECA109 cells, while increasing the expression of connexin26 mRNA and protein; conversely, PPSE decreased Bcl-2 and increased Bad. Conclusion: This study firstly shows that PPSE can increase connexin26 expression at mRNA and protein level, exerting anti-tumour effects on esophageal cacner ECA109 cells via inhibiting cell proliferation and inducing cell apoptosis.

• Korean Journal of Medicinal Crop Science
• /
• v.27 no.6
• /
• pp.365-375
• /
• 2019

Background: Oxidative stress plays an important role in neuro-degenerative disorders such as Alzheimer's disease. Oxidative stress is mediated by reactive oxygen species (ROS), which are implicated in the pathogenesis of numerous diseases, and account for the toxicity of a wide range of compounds. Methods and Results: In order to study the neuro-protective effect of the complex extracts of Aster scaber Thunberg (AS) and Chaenoleles sinensis Koehne (CSK) against hydrogen peroxide in PC12 cells, cell viability was evaluated by the MTT assay using tetrazole, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and the intracellular ROS levels were determined the by 2',7'-dichlorofluorescein diacetate (DCF-DA) assay. In order to examine the anti-amnesic effects of the complex extracts of AS and CSK, behavioral tests were performed on male ICR mice. The ameliorating effect of the complex extracts against Aβ_1-42-induced learning and memory impairment was analyzed by y-maze and passive avoidance tests. The AS and CSK extracts showed neuro-protective activity both in vitro and in vivo, and the neuro-protective effect of their 60 : 40 (AS : CSK) mixture was better than that of the other mixtures. Moreover, the complex extracts synergistically inhibited acetylcholinesterase activity and rapid peroxidation. Conclusions: A mixture of the AS and CSK extracts could be used to develop functional foods and serve as raw materials for the development of therapeutics against Alzheimer's disease.

• Molecules and Cells
• /
• v.24 no.1
• /
• pp.113-118
• /
• 2007

The brains of Alzheimer's disease (AD) patients are characterized by large deposits of amyloid beta peptide ($A{\beta}$). $A{\beta}$ is known to increase free radical production in nerve cells, leading to cell death that is characterized by lipid peroxidation, free radical formation, protein oxidation, and DNA/RNA oxidation. In this study, we selected an extract of Gardenia jasminoides by screening, and investigated its ameliorating effects on $A{\beta}$-induced oxidative stress using PC12 cells. The effects of the extract were evaluated using the 2',7'-dichlorofluorescein diacetate (DCF-DA) assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. To find the active component, the ethanol extract was partitioned with hexane, chloroform, and ethyl acetate, respectively, and the active component was purified by silica-gel column chromatography and HPLC. The results suggested that Gardenia jasminoides extract can reduce the cytotoxicity of $A{\beta}$ in PC 12 cells, possibly by reducing oxidative stress.

• Journal of Microbiology
• /
• v.43 no.2
• /
• pp.213-218
• /
• 2005

Epilepsy constitutes a significant public health problem, and even the newest drugs and neurosurgical techniques have proven unable to cure the disease. In order to select a group of isolates which could generate an active compound with neuroprotective or antiepileptic properties, we isolated 517 actinomycete strains from soil samples taken from Jeju Island, in South Korea. We then screened these strains for possible anti-apoptotic effects against serum deprivation-induced hippocampal cell death, using the 3-(4, 5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay as an in vitro test. The excitotoxic glutamate analog, kainic acid (KA), was used to induce seizures in experimental mice in our in vivo tests. As a result of this testing, we located one strain which exhibited profound neuroprotective activity. This strain was identified as a Streptomyces species, and exhibited the rifampinresistant genotype, Asn$(AAC)^$442, according to the results of 16S rRNA and rpoB gene analyses

• Restorative Dentistry and Endodontics
• /
• v.19 no.2
• /
• pp.409-428
• /
• 1994

Endodontic surgery is performed when conventional endodontic therapy fails or is contraindicated. In such cases, retrograde filling materials including amalgam, composite resin, and various cements have been used. Biocompatibilty and margin sealing ability of retrograde filling materials are important for the long term success of endodontic surgery. In vitro cell culture is frequently used as the method of measuring the biocompatibilty of dental materials. The purpose of this study was to evaluate the cytotoxicity of six kinds of retrograde filling materials including newly developed light curing glass ionomer cements. Each material was mixed according to. the manufacture's instruction and evaluated as : freshly mixed, 24-hour after mixing, and 168-hour after mixing respectively. The elution solution was extracted after 24-hour contact with materials using media. Cytotoxicity was evaluated by direct contact, or elution contact. Test results of radiochromium($^{51}Cr$) release, cell viability using tetrazolium dye (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl dimethyltetrazolium bromide(MTT) test and lactate dehydrogenase(LD) of damaged L929 cells were analyzed. In the $^{51}Cr$ release of direct contact, all experimental retrograde filling materials except amalgam and glass ionomer cement showed increased cytotoxicity compared to control. In the $^{51}Cr$ release of elution solution, the released $^{51}Cr$ was so minimal that it was impossible. to evlauate the cytotoxicity exactly. The elution solutions of glass ionomer cement and IRM showed marked cytotoxicity in MTT test. LD enzyme activity was highest in tests of direct contact with composite, light curing composite, and light curing glass ionomer cement and IRM. Amalgam revealed least cytotoxicity while IRM showed cytotoxicity using all three methods. Composite, light curing composite and light curing glass iomomer cement were cytotoxic in the tests of $^{51}Cr$ release and LD activity. Glass ionomer cement showed cytotoxic effect only in the MTT method. From these results it is suggested that the standardization and optimization of cytotoxicity testing, especially using elution solutions, should be strongly advised.

• Korean Journal of Pharmacognosy
• /
• v.29 no.1
• /
• pp.22-27
• /
• 1998

This study was carried out to develop antitumor agents based on effects of the ethyl acetate soluble fraction of the methanolic extract of Lonicerae flos on human oral epitheloid carcinoma cells. Human oral epitheloid carcinoma cells were cultured in RPMI-1640 media containing 10% fetal bovine serum, antibiotic, and fungizone. After incubation for 24 hrs, the cells were treated with A, B, C, D, and E fractions for 48hrs under the same condition. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide), NR (Neutral red) and SRB (Sulforhodamine B protein) assay were performed. The light microscopic findings were observed by inverted microscope. In MTT assay, fraction B was shown significant antitumor activity (P<0.001), fraction E was shown significant antitumor activities (P<0.05), but the other fractions were not shown. In NR assay, fraction B was shown significant antitumor activity (P<0.001). In SRB assay, fractions B was shown significant antitumor activities (P<0.01). fractions A and D were shown significant antitumor activities (P<0.05). but the other fractions were not shown. In light microscopy. the fraction B of the ethyl acetate soluble fraction of the methanolic extract of Lonicerae flos showed the highest antitumor activity. These finding suggested that fraction B possessed the most antitumorous agent.