Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.
Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the aglycone derivatives of major ginsenosides, has been shown to have an anticancer activity toward a variety of cancers. This study was initiated with an attempt to evaluate its anti-cancer activity toward human endometrial cancer by cell and xenograft mouse models. Methods: Human endometrial cancer (HEC)-1A cells were incubated with different 20(S)-PPD concentrations. 20(S)-PPD cytotoxicity was evaluated using MTT assay. Apoptosis was detected using the annexin V binding assay and cell cycle analysis. Cleaved poly (ADP-ribose) polymerase (PARP) and activated caspase-9 were assessed using western blotting. HEC-1A cell tumor xenografts in athymic mice were generated by inoculating HEC-1A cells into the flank of BALB/c female mice and explored to validate 20(S)-PPD anti-endometrial cancer toxicity. Results: 20(S)-PPD inhibited HEC-1A cell proliferation in a dose-dependent manner with an IC50 value of 3.5 μM at 24 h. HEC-1A cells morphologically changed after 20(S)-PPD treatment, bearing resemblance to Taxol-treated cells. Annexin V-positive cell percentages were 0%, 10.8%, and 58.1% in HEC-1A cells when treated with 0, 2.5, and 5 μM of 20(S)-PPD, respectively, for 24 h. 20(S)-PPD subcutaneously injected into the HEC-1A cell xenograft-bearing mice three times a week for 17 days manifested tumor growth inhibition by as much as 18% at a dose of 80 mg/kg, which sharply contrasted to controls that showed an approximately 2.4-fold tumor volume increase. These events paralleled caspase-9 activation and PARP cleavage. Conclusion: 20(S)-PPD inhibits endometrial cancer cell proliferation by inducing cell death via a caspase-mediated apoptosis pathway. Therefore, the 20(S)-PPD-like ginsenosides are endowed with ample structural information that could be utilized to develop other ginsenoside-based anticancer agents.
Journal of the Korean Applied Science and Technology
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v.37
no.2
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pp.153-161
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2020
Arthrospira platensis is the oldest marine microalgae on the planet, is said to contain most of the nutrients needed by the human body. It's components are reported to contain a large amount of various substances such as phycocyanin, chlorophyll and β-carotene, and are known to have an aging and whitening effect. In this study, UVB-induced reactive oxygen species reduction efficacy and antioxidant activity of spirulina purified water extract were investigated. effect was confirmed by measuring DPPH radical scavenging activity, FRAP reducing power and ABTS+ radical scavenging activity of 0.05, 0.10, 0.50 1.0 mg/mL of spirulina purified water extract. The coagulation rate, hatching rate and heart rate toxicity were measured by treating spirulina purified water extract with 0.05, 0.10, 0.50 mg/mL concentration using Zebrafish, an alternative experimental animal model. UVB-induced ROS measurement was treated with spirulina extract at 0.05, 0.10, 0.50 mg/mL concentration, and then stained with DCFH-DA to confirm the inhibitory effect of ROS. As a result of measuring antioxidant effect, DPPH, FRAP and ABTS+ showed concentration-dependent antioxidant effects in comparison with ascorbic acid. and measuring the coagulation rate, hatching rate, and heart rate using Zebrafish, an alternative experimental animal, it was confirmed that there was no toxicity in 0.05 and 0.10 mg/mL except 0.5 mg/mL compared to the control group. The ROS scavenging activity of UVB-induced zebrafish showed higher ROS reduction than the positive control. The results of this study suggest that spirulina and purified water extracts are valuable for UV and skin protection cosmetics.
This study was demonstrate a repeated oral dose toxicity of detoxication sulphur in 8-weeks-old female Sprague-Dawley (SD) rats. The rats were treated with dose of 0.2%, 1%, 5% detoxication sulphur and 1% sulphur of feed consumption administered for 13 weeks. To evaluate the safety of detoxication sulfur, we examined the body weight, the feed intake, the clinical signs, the ophthalmological test, the hematological and the serum biochemical analysis. We also observed the histopathological changes of liver and kidney in rats. As a result, no significant differences in body weight, feed intake, hematological examination and histopathological between control and detoxication sulphur treatment group were found. Serum biochemical results were not shown significant differences in 0.2% and 1% the treated groups compared with control group. But glucose level were decrease, also ALT and ALP level were increase in 5% treated group. All of these results indicate that 1% detoxication sulphur of feed consumption may be safety in SD rat.
Recently, use of natural medicine is getting more attention, and some of them are believed to be effective in the treatment of periodontitis. Among them, the seeds of safflower(Carthamus tinctrorius L.) have been proven to be effective through its use in bone diseases such as fracture and osteoporosis. During the last few years, studies using the seeds of safflower gown in Korea have been active, and it has been reported that safflower seed extract increase the proliferation and the alkaline phosphatase(ALP) activity of human periodontal ligament fibroblast(hPDLF), osteoblast, and that they promote the mineralization process. In animal studies, when safflower seed extract were administered orally new bone formation was promoted. Recently, in an effort to find out the most effective osteogenic components, among many components of the safflower seed, various safflower seed fraction extracts were obtained by multistep extraction of the safflower components using various solvents. Among these, saf-M-W fraction extracted by methanol and water was most effective in increasing osteogenic potential of osteoblasts. In this study, the effect of safflower seed fraction extract, saf-M-W, on the growth and differentiation of hPDLF and MC3T3-E1 cell was investigated. The toxicity of saf-M-W on both cells was measured using M'IT(3-(4,5dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide) test, and ALP activity was measured using the colorimetric assay of hPDLF. In addition, in MC3T3-El cells, the expression of ALP, bone sialoprotein(BSP) mRNA was observed using Northern blot, and the mineralized nodule formation Was observed using von Kossa stain and phase-contrast microscope. 1. In concentrations below $10{\mu}g/ml$, saf-M-W didn't show any toxicity on hPDLF and MC3T3-El cell. 2. The change in saf-M-W concentration had no effect on the ALP activity of hPDLF. 3. In MC3T-E1 cells, mRNA expressions of ALP and BSP were greater in the experimental group treated with $10{\mu}g/ml$ concentration of saf-M-W compared with the control group. 4. In MC3T3-El cells, abundance of mineralized nodules were formed in the experimental group treated with $10{\mu}g/ml$ Concentration of saf-M-W, while no mineralized nodule was formed in the control group. These results suggest that safflower seed fraction extract, saf-M-W. didn't show any toxicity on hPDLF and MC3T3-E1 cell at concentrations below $10{\mu}g/ml$ and effectively enhanced the differentiation and osteogenic potential of MC3T3-El cell.
Kim, Young Ryun;Kim, Tae Won;Son, Min Ho;Oh, Sangwoo;Lee, Moonjin
Journal of the Korean Society of Marine Environment & Safety
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v.21
no.6
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pp.672-678
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2015
The types of hazardous and noxious substances (HNS) being transported by sea in Korea are at about 6,000, HNS transport volume accounts for 19% of total tonnage shipped in Korea, and the increase rate of seaborne HNS trade in Korea is 2.5 times higher than the average increase rate of the world seaborne HNS trade. Reflecting this trend, HNS spill incidents have been frequently reported in Korean waters, and there are increasing social demands to develop HNS management technology for the preparedness, response, post-treatment and restoration in relation to HNS spill incidents at sea. In this study, a risk-based HNS prioritization system was developed and an HNS risk database was built with evaluation indices such as sea transport volume, physicochemical properties, toxicities, persistency, and bioaccumulation. Risk scores for human health and marine environments were calculated by multiplying scores for toxicity and exposure. The top-20 substances in the list of HNS were tabulated, and Aniline was ranked first place, but it needs to be managed not by individuals but by HNS groups with similar score levels. Limitations were identified in obtaining data of chronic toxicity and marine ecotoxicity due to lack of testing data. It is necessary to study on marine ecotoxicological test in the near future. Moreover, the priority list of HNS is expected to be utilized in the development of HNS management technology and the relevant technologies, after the expert's review process and making up for the lack of test data in the current research results.
Hwang-Bo, Hyun;Kwon, Da Hye;Kim, Min Young;Ji, Seon Yeong;Choi, Eun Ok;Kim, Sung Ok;Jeong, Ji-Suk;Hong, Su Hyun;Choi, Sung Hyun;Park, Cheol;Choi, Yung Hyun
Journal of Life Science
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v.29
no.1
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pp.112-117
/
2019
Herbal medicines are widely used as therapeutic products in many countries. Corni fructus (CF), the dried ripe sarcocarp of Cornus officinalis Sieb. et Zucc (Cornaceae), has been used for thousands of years in traditional medicine and has been reported to be effective for the prevention and treatment of various diseases, such as kidney diseases and diabetes. Recent research on CF has documented a wide spectrum of therapeutic properties, which include anti-inflammatory, ant-oxidative, immunomodulatory, and anti-cancer effects. However, there is no information on its safety. Therefore, in this study, the toxicity of water extract of CF to ICR mice was investigated. The mice received a single dose of water extract of CF (1,000, 2,000, and 5,000 mg/kg of body weight) via the oral route. Mortality, clinical signs, body weight changes, gross findings, and weights of the principal organs after 14 d were then assessed. The results revealed no adverse effects of CF as determined by clinical signs, body weights, or organ weights and no gross pathological findings in any of the treatment groups. These results suggest that the 50% lethal dose and approximated lethal dose of CF extract is over 5,000 mg/kg. The findings provide scientific evidence for the safety of CFs.
Kim, Jong Cheon;Ryu, Young;Hong, Yeon Heui;Kim, Seok Chan
Applied Chemistry for Engineering
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v.25
no.5
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pp.548-551
/
2014
In order to reduce toxicity on the human body, four new cleaning agents (1-4) containing ester and ether functionalities have been invented. The synthesized cleaning agents's physical properties, biodegradabilities, and $LD_{50}$ values, which were conducted by Korea Testing Certification Institute by using standard method, showed excellent values. A specimen for cleaning ability was prepared by cutting in $60{\times}40mm$ size of stainless steel plate. The surface of the above specimens was treated with four different kinds of contaminants, such as cutting oil, anti-rust oil, drawing oil, and lubricating oil. Contaminated specimens were then immersed in compounds (1-4) for 1 to 5 minutes to dissolve oil in the cleaning agent. The data indicate that all compounds (1-4) exhibit good cleaning ability toward four contaminant oils. It is also confirmed that these compounds can be applicable to various industrial cleaning fields as nontoxic and biodegradable cleaning agents because of their excellent biodegradabilities and $LD_{50}$ values.
Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are the most concerned toxic organic pollutants to human. Because of their extremely high toxicity and uncertain genotoxic potential, their determination in environmental and biological samples is of great interest. Municipal solid waste incinerator facilities have been reported as the major contributors of dioxins and furans to the environment, and their formation from combustion is a universal phenomenon, everywhere. In this study dioxins and furans were analyzed from the bottom ash produced during combustion in an municipal waste incinerator located in Seoul. The EPA method was modified for sample pretreatment: the soxhlet method was used for extraction and clean-up procedures were performed by using silica and basic alumina, excluding active-carbon. The extract was then analyzed by HRGC/HRMS. A general trend of increase in the amounts of 6∼7 chlorine-substituted dioxins and furans was observed. Total dioxins, furans and 2,3,7,8-TCDD were determined as 8.05 ng/g, 4.75 ng/g, and 6.93 pg/g, respectively.
The Korean groundwater law regulates 20 groundwater contamination parameters, including 14 specific harmful substances. Expanding the number of groundwater quality standards are needed to cope with recent groundwater quality deterioration due to the use of various chemicals. Chemical ranking and scoring system (CRS) is a scientific tool to sort priority chemicals by considering exposure and toxicity potentials. In this study, we developed a CRS for scoring and ranking of possible groundwater pollutants and screened priority substances to be later considered in the Korean standard expansion. Chemical Ranking Of groundWater pollutaNts (CROWN) incorporates important parameters consisting of exposure potential, human and water ecotoxicity, interests, and certainty. Furthermore, CROWN additionally evaluated existence of other media standards to consider impacts by contamination of other media. The 197 substances that were common to 9 countries were selected first. CROWN evaluated and ranked each chemical, and finally suggested priority substances. Suggested priority substances were classified into two groups according to the groundwater use purposes: drinking and non-drinking. The priority substances were further classified into $1^{st}$ and $2^{nd}$ group priorities. The $1^{st}$ group consists of 75 substances, including the all the Korean groundwater standard parameters. CROWN will be used in selecting groundwater pollutants for possible inclusion in the Korean standard expansion.
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