• Journal of Life Science
• /
• v.20 no.5
• /
• pp.760-767
• /
• 2010

The oxidative damage of lipids, protein, and DNA is known to be involved in not only chronic inflammations such as arthritis, hepatitis, nephritis, gastritis, colitis, and periodontitis but also metastasis. It has given impetus to searching for natural compounds without toxicity, which prevent the development of these diseases. The direct scavenging effects of aged black garlic extract (ABGE) were evaluated in vitro on DPPH radical, hydroxyl radical, hydrogen peroxide, and genomic DNA damage related to oxidative stress. Furthermore, its antioxidant effect on lipid peroxidation was investigated in human fibrosarcoma cells (HT1080), which were exposed to the hydroxyl radical generated by the Fenton reaction. It was observed that ABGE exhibited a greater inhibitory effect on hydrogen peroxide than other reactive oxygen species, and also blocked DNA oxidation and lipid peroxidation induced by the hydroxyl radical. The oxidative stress in live cells was also inhibited in the presence of ABGE. In addition, its inhibitory effects on the activity and expression of MMP-2 and -9 related to metastasis were determined using gelatin zymography and western blot. The data showed that it inhibited MMP-2 and -9 in PMA-stimulated HT1080 cells. Therefore, these results suggest that ABGE show potential as an excellent agent for prevention of metastasis related to oxidative stress.

• Journal of Life Science
• /
• v.24 no.6
• /
• pp.700-706
• /
• 2014

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.

• Journal of Life Science
• /
• v.27 no.12
• /
• pp.1470-1478
• /
• 2017

The aim of this study was to investigate biological activity and biochemical properties of extracts from Bacillus subtilis-fermented silkworm (Bombyx mori L., SP) powder of different origin (Buan, Namwon, and Boeun). An additional aim was to determine the inhibition of cancer cell (B16-F10, HT-29, LNcaP, and MCF-7) proliferation and nitric oxide (NO) production from lipopolysaccharide (LPS)-induced RAW264.7 cells. Biological activities (${\alpha},{\alpha}^{\prime}$-diphenyl-${\beta}$-picrylhydrazyl [DPPH], free radical scavenging activity, fibrinolytic activity, antiproliferation activity, and anti-inflammatory activity) and biochemical properties (compositional amino acid contents, and mineral contents) were examined in water extracts from silkworm powder and B. subtilis-fermented silkworm powder. The highest amino acid contents were detected in Buan silkworm powder (BU). After fermented, the highest contents were found in B. subtilis-fermented Buan silkworm powder (BBO). The major minerals detected were K, Ca, and Mg. Rates of these minerals, especially those of Na increased after fermented. DPPH radical scavenging activity and fibrinolytic activity were stronger in the fermented group than non-fermented group. DPPH radical scavenging activity and fibrinolytic activity were highest in the extract from BBO. The inhibition activities of LNcaP and MCF-7 cells viability were significantly decreased in the BBO, and there was no inhibition activity in other cancer cells (B16-F10 and HT-29). An SRB assay of the cell viability of RAW 264.7 cells exposed to extracts of silkworm powder and B. subtilis-fermented silkworm powder revealed no toxicity in any of the groups. Compared with the LPS-treated group, the biggest reduction in NO production was detected in the BBO group. Based on these results, extracts from Boeun silkworm powder fermented with B. subtilis could be a candidate material as a dietary supplement for use in healthy functional foods.

• Molecules and Cells
• /
• v.40 no.8
• /
• pp.567-576
• /
• 2017

The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.

• Weed & Turfgrass Science
• /
• v.4 no.2
• /
• pp.104-110
• /
• 2015

This study was conducted for 3 years in an apple orchard to investigate the efficacy of the glufosinate-ammonium (GFA) SL for weed control in comparison to non-woven fabric mulch, sod culture and machinery cutting treatments. Glufosinate-ammonium SL 18% was applied with 2 to 3 times, and the extents of injury caused by the different weed control methods were also investigated during the 3 years. The highest level of weed control was obtained by glufosinate-ammonium 3 times spray (98.7%), followed by machinery cutting (95.1%), glufosinate-ammonium 2 times spray (81.5%) and natural sod culture (5.8%). Amounts of fruit production in three times application of glufosinate-ammonium 540 g a.i. $ha^{-1}$, twice application of GFA, machinery cutting, non-woven fabric processing, sod culture and untreated control were 27.2, 26.2, 25.3, 24.1, 20.4 and 13.3 kg, respectively. There was no toxicity symptom of glufosinate-ammonium on the whole tree such as fruit, bud, trunk, branch and flower during the 3 years.

• Korean Journal of Medicinal Crop Science
• /
• v.15 no.6
• /
• pp.437-443
• /
• 2007

This study was carried out to investigate the effect of dietary supplementation with red ginseng water-extracts on the induction of microsomal cytochrome P-450 in rats. Phenobarbital (PB) and 3-methylcholanthrene (3-MC), P-450 inducers, were administered to 3- or 12-month old rats received red ginseng extracts (25 mg/kg) from 6 weeks to 12 months for 3 days. PB and 3-MC increased levels of P-450, P-450 reductase, ethoxycoumarin O-deethylase, benzphetamine N-demethylase and glutathione-S-transferase in the liver of rats. However, chronic administration of red ginseng significantly reduced these increase of enzyme levels induced by P-450 inducers. Chronic administration of red ginseng did not affect the induction of cytochrome $b_5$ and NADH cytochrome $b_5$ reductase by P-450 inducers. It is suggested that the induction of cytochrome P-450 system in the liver in relation to xenobiotics toxicity can be modulated by long-term supplementation with Korean red ginseng to rats.

• Tuberculosis and Respiratory Diseases
• /
• v.69 no.2
• /
• pp.115-118
• /
• 2010

Paclitaxel has been widely used for treating many solid tumors. Although colonic toxicity is an unusual complication of paclitaxel-based chemotherapy, the reported toxicities include pseudomembranous colitis, neutropenic enterocolitis and on rare occasions ischemic colitis. $Genexol-PM^{(R)}$, which is a recently developed cremophor-free, polymeric micelle-formulated paclitaxel, has shown a more potent antitumor effect because it can increase the usual dose of paclitaxel due to that $Genexol-PM^{(R)}$ does not include the toxic cremophor compound. We report here on a case of a 57-year-old man with advanced non-small cell lung cancer and who developed ischemic colitis after chemotherapy with $Genexol-PM^{(R)}$ and cisplatin. He complained of hematochezia with abdominal pain on the left lower quadrant. Colonoscopy revealed diffuse mucosal hemorrhage and edema from the sigmoid colon to the splenic flexure. After bowel rest, he recovered from his symptoms and the follow-up colonoscopic findings showed that the mucosa was healing. Since then, he was treated with pemetrexed monotherapy instead of a paclitaxel compound and platinum.

• Korean Journal of Clinical Pharmacy
• /
• v.19 no.1
• /
• pp.18-22
• /
• 2009

Oxaliplatin is a tolerable and effective drug of choice in the treatment of advanced or metastatic gastric cancer. However, it has many dose-limiting neurotoxicities. This study was performed to assess the incidence and types of oxaliplatin-related neurotoxicities. Sixty-four patients receiving oxaliplatin-involved regimen as salvage therapy on metastatic gastric cancer or as the first-line therapy on advanced gastric cancer were evaluated during the period between September 1, 2006 and February 29, 2008. The patients were treated with oxaliplatin 100 $mg/m^2$ and leucovorin 100 $mg/m^2$ simultaneously as 2-hour-lasting infusion on Day-1 followed by 5-FU 1200 $mg/m^2$ as a 22-hour-lasting continuous infusion both on Day-1 and Day-2 by every other week. We developed questionnaires to evaluate patient-recognized neurotoxic symptoms rather than the observer-described events. Surveys were completed at bedside or via telephone interview. Acute and chronic neurotoxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC, version 3) as well as the Oxaliplatin-specific Neurotoxicity Scale. The Grade-3 neuropathy was reported in 19% of the patients (n=12) and grade-1/2 neuropathy occurred in 70% (n=45). The most common symptom was cold-related dysesthesia (83%) regarded as nociperception by the patients. Some patients (19%) experienced functional impairment affecting activities of daily living such as writing, buttoning, and walking. Even though 74% of the patients (42/57) were prescribed with gabapentin to reduce these peripheral symptoms, it did not appear to derive any benefit from this medication. It is suggested that notify the patients about their oxaliplatin-associated, debilitating symptoms, and educate them any self-care strategy at the initiating phase of the chemotherapy. Moreover, it needs to design the intervention studies regarding the prevention and management of the peripheral neuropathy.

• Korean Journal of Clinical Pharmacy
• /
• v.24 no.4
• /
• pp.231-239
• /
• 2014

Background and objective: Pravastatin has been shown to have favorable risk-benefit profile when it is administered to hypercholesterolemic subjects to prevent cardiovascular events. However, subjects with impaired OATP1B1 activity may be more susceptible to pravastatin-induced muscle toxicity than subjects with normal OATP1B1 activity. A systematic review was conducted to evaluate the effect of SLCO1B1 genetic polymorphism on pharmacokinetics of pravastatin. Method: Medline$^{(R)}$ and Embase$^{(R)}$ were searched for relevant studies until July 2013. The search terms used were pravastatin AND (SLCO1B1 OR OATP1B1 OR LST1 OR SLC21A6) AND (gene OR $genetic^*$ OR $genomic^*$ OR $pharmacogenet^*$ OR $pharmacogenom^*$ OR $polymorph^*$). Results: A meta-analysis of the area under the concentration-time curve (AUC) of pravastatin in $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ was conducted. Five studies met all the inclusion criteria and methodological requirements. There was no statistically significant difference in the AUC value between $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ (p=0.728). However, $SLCO1B1^*15$ participants exhibited significantly higher AUC values than $SLCO1B1^*1b/^*1b$ carriers (p<0.001). In case of $SLCO1B1^*15^*15$ carriers, they had significantly higher AUC value than $SLCO1B1^*1a/^*1a$ subjects (p=0.002). Lastly, compared with to the subjects of $SLCO1B1^*1a/^*1a$, the carriers of heterozygous $SLCO1B1^*15$ increased the AUC value of pravastatin statistically significantly in Asian population (p=0.014). Conclusion: The present meta-analysis suggests that subjects with $SLCO1B1^*15$ are associated with increased AUC of pravastatin.

• Journal of the Korea Convergence Society
• /
• v.11 no.5
• /
• pp.241-251
• /
• 2020

This study was performed to develop the cosmetics containing extract of U.davidiana, which has been confirmed as a functional ingredient of anti-microbial, anti-oxidant, and anti-inflammatory effects, and also to evaluate the improvement effects of dry and sensitive skin such as atopic dermatitis. Toxicity tests of the Ulmus davidiana supercritical fluid residue 60% EtOH extracts(USCFR), Ulmus davidiana supercritical fluid extracts(USCF) and preliminary formulations, DKBP-1903(gel), containing the USCFR and USCF were determined to be 'Non-toxic'. Based on this, the stability test of the lotion, cream, gel formulation was conducted and the results showed that cream and gel formulation were stable. A 48-hour moisturizing sustainability test and the improvement test on the pruritus caused by dryness were selected for the cosmetic efficacy test to evaluate the improvement of atopic dermatitis and as a result both cream and gel have been found to be relatively safe moisturizers that can help dry and sensitive skin.