• Bulletin of the Korean Chemical Society
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• v.35 no.5
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• pp.1294-1298
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• 2014

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer representing 85% of lung cancer patients. Despite several EGFR-targeted drugs have been developed in the treatment of NSCLC, the clinical efficacy of these EGFR-targeted therapies is being challenged by the occurrence of drug resistance. In this regard, Hsp90 represents great promise as a therapeutic target of cancerous diseases due to its role in modulating and stabilizing numerous oncogenic proteins. Accordingly, inhibition of single Hsp90 protein simultaneously disables multiple signaling networks so as to overcome drug resistance in cancer. In this study, we synthesized a series of 11 butein analogues and evaluated their biological activities against gefitinibresistant NSCLC cells (H1975). Our study indicated that analogue 1h inhibited the proliferation of H1975 cells, down-regulated the expression of Hsp90 client proteins, including EGFR, Met, Her2, Akt and Cdk4, and upregulated the expression of Hsp70. The result suggested that compound 1h disrupted Hsp90 chaperoning function and could serve a potential lead compound to overcome the drug resistance in cancer chemotherapy.

• Journal of Environmental Science International
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• v.26 no.11
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• pp.1285-1295
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• 2017

Chrysanthemum boreale Makino is widely distributed in Korea, China, Japan and Southeast Asian countries. C. boreale is one of the herbs used for treating various inflammatory diseases in oriental medicine. The present study was conducted to identify biologically active compounds from the leaves and stems of C. boreale. We isolated two sesquiterpene sactones from the leaves and stems of C. boreale using silica gel column chromatography and recyclic high perfomance liquid chromatography. The lactones were characterized by their spectroscopic data (NMR, IR, MASS). These compounds were subjected to Farnesyl Protein Transferase (FPTase) inhibition, Nitric Oxide (NO) release inhibition and apoptosis inhibition. The structur of the following isolated compound were elucidated 8,10-${\small{O}$-Acetyl-2-methoxy-10-hydroxy-3,11(13)-guaiadiene-12,6-olide and 4,10-dihydroxy-8-${\small{O}$-Acetyl-2,11(13)-guaiadiene-12,6-olide. In the NO release inhibition assay, compound 2 showed strong activities, with an $IC_{50}$ value of $7{\mu}g/mL$, whereas compound 1 did not exhibit significant activity with an $IC_{50}$ value of over $14{\mu}g/mL$ against murine macrophage.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.1
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• pp.112-117
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• 2013

We studied the modulation of pacemaker activities by Samchulkunbi-tang (SCKB) in cultured interstitial cells of Cajal (ICC) from murine small intestine with the whole-cell patch-clamp technique. Externally applied SCKB produced membrane depolarization in the current-clamp mode. The pretreatment with $Ca^{2+}$-free solution and thapsigargin, a $Ca^{2+}$-ATPase inhibitor in endoplasmic reticulum, abolished the generation of pacemaker potentials and suppressed the SCKB-induced action. The application of flufenamic acid (a nonselective cation channel blocker) abolished the generation of pacemaker potentials by SCKB. However, the application of niflumic acid (a chloride channel blocker) did not inhibit the generation of pacemaker potentials by SCKB. In addition, the membrane depolarizations were inhibited by not only GDP-${\beta}$-S, which permanently binds G-binding proteins, but also U-73122, an active phospholipase C inhibitor. These results suggest that SCKB modulates the pacemaker activities by nonselective cation channels and external $Ca^{2+}$ influx and internal $Ca^{2+}$ release via G-protein and phospholipase C-dependent mechanism. Therefore, the ICC are targets for SCKB and their interaction can affect intestinal motility.

• Journal of Nutrition and Health
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• v.31 no.2
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• pp.117-125
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• 1998

Mulberry leaves(Mori folium) and silkworm(Bombyx mori) are potnet inhibiters of intestinal $\alpha$-glycosidase, and inhibit the digestion of starch and sucrose in the small intestine. They are able to prevent postprandial hyperglycemia and decrease blood insulin levels. In this study , a high-carbohydrate diet(CHO ; 67.5%, protein ; 20.8%, fat : 11.7%) was received by the control group. In contrast, the experimental groups received a high-carbohydrate diet with extracts of mulberry leaves and silkwork(50mg.100g diet), and acarbose(6.7mg/100g diet). after a 10 week study period , the experimental groups had lower blood glucose and triglyceride levels. The experimental groups tended to have lwer Hb Alc levels. Also, blood insulin levels were lower than the control groups in accordance with blood glucose levels. The activities of intestinal $\alpha$-glucosidase in the middle and distal parts of small intestine were induced by the extracts of mulberry leaves and silkworm in the experimental groups. However, the activities of liver lysosomal glucosidase and the contents of glycogen in the liver were not affected by the mulberry leave and silkworm extracts nor by acarbose. Mulberry leaves and silkworm were able to prevent sudden postprandial peaks in blood glucose as a result of $\alpha$-glycosidase, inhibition, there by decreasing unnecessary insulin secretion.

• Interdisciplinary Bio Central
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• v.4 no.4
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• pp.13.1-13.6
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• 2012

The advanced glycation endproducts receptor (AGER) is a multiligand signal transduction receptor. One of its ligands, S100b molecules activates vascular smooth muscle cells and endothelial cells via its receptor, thus triggering activation of signaling cascades and generation of cytokines and proinflammatory molecules. Ubiquitin-conjugating enzyme Ubc9 is an E2 conjugating enzyme that transfers the activated small ubiquitin-related modifier to protein substrates, and thus it plays a critical role in SUR-Mylation-mediated cellular pathways. Previous studies have shown that both AGE-R and Ubc9 play roles in diverse cellular signaling pathways. However, until recently, little attention has been paid to interactions between AGE-R and Ubc9. In this study, sequence database searches allowed us to identify a potential interaction motif between AGE-R and Ubc9. The subsequent biochemical and molecular biological analysis suggested that there may be specificity in AGE-R and Ubc9 complex signaling in atherosclerosis and cancer cells in a cell-type specific manner. Although the determinant for specificity in AGE-R and Ubc9 complex signaling in cancer cells and atherosclerosis is yet to be determined, this study provides the basis to develop a specific therapeutic application of AGE-R, SURM (small ubiquitin-related modifier)-1, and Ubc9 complex activation pathways in atherosclerosis, diabetes, cancer and inflammatory diseases.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.12
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• pp.1773-1778
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• 2008

Two experiments were carried out to study the effects of corticosterone (CORT) administration on intestinal morphology and function of broilers. In both experiments, birds were randomly divided into two equal groups. One group was the control group (CTRL), and the birds were fed with a basal diet. The other was the experimental group (CORT), and the birds were fed with the basal diet plus 30 mg of CORT/kg diet. At 21 days of age, performance, morphological characteristics of intestine, D-xylose level in plasma, activities of digestive enzymes in digesta, digestibility of nutrients and 5-bromo-2-deoxyuridine (BrdUrd)-labeling index of intestinal epithelial cells were determined. CORT administration decreased feed intake, daily gain and feed conversion ratio (p<0.05). CORT also decreased duodenal and jejunal villus height (p<0.05) as well as crypt depth (p<0.05). The D-xylose level in plasma of CORT-treated broilers was lower than that of the control (p<0.05). CORT treatment caused a decrease in apparent digestibility of protein (p<0.05), whereas fat and starch apparent digestibilities were unaffected (p>0.05). CORT administration increased activities of trypsin and amylase (p<0.05), and decreased BrdUrd-labeling index of duodenal and jejunal epithelial cells (p<0.05). In conclusion, CORT administration impaired the normal morphology and absorptive capacity of the small intestine of broiler chickens.

• Journal of the Korean Home Economics Association
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• v.28 no.2
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• pp.31-36
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• 1990

This studies were conducted to find out the possibility of utilizing red pepper seed as resources of food fats, the research method was designed to make a comparison between crude and refined oil, and the results of the studies are as follows : The red pepper seed contained 28% of crude fat and 21% of crude protein. The main fatty acids of red pepper seed oil were linoleic acid(72.10~72.31%), palmitic acid(12.81~13.28%) and oleic acid(9.47~10.48%). The linolenic acid content was so small that is will not influence the autoxidation of the red pepper seed oil. The major triglyceride type of crude and refined oil of red pepper seeds were C52 and C54. The other types were found in a small quantity. The sterol composition of crude oil was $\beta$-sitosterol, campasterol, stigmasteral and brassicasterol,in the quantity order. after refining, brassicasterol was not detected, and the content was decreased by one six and one eight. The toropherol composition of crude and refined oil, tocopherol analog was composed of three kinds $\alpha$-, ${\gamma}$-, $\delta$-, but no $\beta$-form. the quantity of ${\gamma}$-, $\alpha$- and $\delta$-tocopherol were 162.91, 83.72, 43.98mg% respectively. The Quantity of and capsaicin in crude oil was 1,296 ppm, and it was reduced consicerably by refining and removed completely after the process of redeodorization.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4391-4394
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• 2016

Background: Platinum-based regimens are effective treatments for advanced non-small cell lung cancer (NSCLC), but the five-year survival rate is still less than 20%. One possible factor appears to be resistance involving polymorphisms in the CTR1 gene which plays an importance role in accumulation of platinum in the cytoplasm. Purpose: To establish both prevalence of CTR1 polymorphism and its impact on treatment related toxicity in Thai advanced NSCLC patients. Materials and Methods: Thirty-two advanced NSCLC participants received carboplatin and gemcitabine during January to June 2016 at King Chulalongkorn Memorial Hospital (KCMH) were recruited for analysis of the CTR1 rs12686377 genotype. These participants were planning to be treated with platinum-based chemotherapy for at least two cycles. Results: Allele frequency of CTR1 polymorphism $G{\rightarrow}T$ was found to be 25%. The results showed that genetic polymorphism at CTR1 rs12686377 was associated with emesis side effects (P = 0.020) and neuropathic symptoms (P = 0.010). In addition, hematologic side effects in terms of anemia also tended to be related to this polymorphism. Conclusions: This is the first study suggesting that polymorphism at CTR1 rs12686377 may be associated with toxicity from platinum-based regimens. Therefore, it could be a factor to aid in treatment decision-making.

• Tuberculosis and Respiratory Diseases
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• v.71 no.5
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• pp.349-354
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• 2011

Background: Lung cancer is the leading cause of cancer deaths in the world. Human papillomavirus (HPV) infection and E6 oncoprotein expression are known risk factors for the development of non-small cell lung cancer (NSCLC). This study was performed to evaluate the prevalence of HPV 16/18 E6 oncoprotein expression in patients with NSCLC. Methods: Immunohistochemical stains of the HPV 16/18 E6 oncoprotein were performed in tumor tissues from 68 patients with NSCLC who underwent curative surgery from March 2006 to November 2008. Results: The E6 oncoprotein was expressed in 29.4% of patients with NSCLC and a statistical analysis revealed that E6 oncoprotein expression was significantly higher in females (p=0.028), never smokers (p=0.045), and patients with adenocarcinoma (p=0.022) than that in other patients. Conclusion: The E6 oncoprotein was expressed in 29.4% of patients with NSCLC. Further studies detecting HPV infection and E6 oncoprotein expression in never smoking patients with NSCLC are needed.

• Parasites, Hosts and Diseases
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• v.52 no.4
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• pp.439-441
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• 2014

Toxoplasma gondii is the causative agent of toxoplasmosis with symptoms of congenital neurological and ocular diseases and acquired lymphadenitis, retinochoroiditis, and meningoencephalitis. Small molecules which block the activity of protein kinases were tested in in vitro culture of T. gondii to find new therapeutic drugs of safer and more effective than the combined administration of pyrimethamine and sulfadoxine that sometimes provoke lethal Stevens-Johnson syndrome. Among them, Gefitinib and Crizotinib inhibited intracellular growth of T. gondii in HeLa cells by counting the number of T. gondii per parasitophorous vacuolar membrane whereas Sunitinib did not. Gefitinib inhibited the growth of T. gondii in a dose-dependent manner over $5{\mu}M$ up to the tolerable concentration of HeLa cells and halted the division of the parasite immediately from the time point of treatment. Gefitinib inhibition suggests that tyrosine kinases of EGFR family or other homologous kinases of the parasite itself may be the target to cause the block of T. gondii growth.