• Bulletin of the Korean Chemical Society
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• 제31권7호
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• pp.1848-1858
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• 2010

Phenylaminopyrimidines represent a large group of new selective anticancer agents, the majority of which exert their action through the inhibition of specific kinases. In this study, a new series of N-substituted-2-aminopyrimidines has been designed and synthesized. A selected group of the synthesized derivatives was screened at a single dose concentration of 10 ${\mu}M$ over a panel of 60 cancer cell-lines. Compound 12e has showed great inhibitory and strong lethal effect over almost all of the 60 cell-lines and accordingly was further tested in a 5-dose testing mode to determine its $IC_{50}$ values, where it showed great efficacies with intermediate potencies over the tested cell-lines. The compound was also tested over a panel of 52 kinases to explore its kinase inhibitory profile, and was found to be a selective but moderate inhibitor over FLT3 kinase.

• 한방안이비인후피부과학회지
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• 제14권1호
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• pp.154-166
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• 2001

Naesosan(NSS) has been used in Oriental Medicine as a drug that treated carbuncle and cellulitis. So, the purpose of this Study was to investigate effects of NSS on the cytotoxicity of cancer cell lines and lymphocytes in vitro, proliferation of Ll210 cells and lymphocytes in L1210 cells transplanted mice, improvement of blood count in Ll210 cells transplanted mice, tumor weight and body weight in sarcoma-180 cells transplanted mice, survival prolongation in sarcoma-180 cells transplanted mice. We used NSS extract with freeze-dried, 8wks-old male mice(balb/c and ICR mouse $18{\pm}2g$). Ll210 cell lines, and sarcoma-180 cell lines for this Study, The proliferation of cells was tested using a colorimetric tetrazoliun assay(MTT assay). The results of this Study were obtained as follows ; 1. NSS showed significantly cytotoxicitic effects of cancer cell lines, did not show cytotoxicitic effects of lymphocytes. 2, Proliferation of lymphocytes in L1210 cells transplanted mice did not effects by NSS. 3. NSS inhibited significantly the proliferation of L1210 cells in L1210 cells transplanted mice. 4. NSS improved significantly the blood count in Ll210 cells transplanted mice. 5. NSS increased significantly th body weight in sarcoma-180 cells transplanted mice. 6. NSS dereased significantly the tumor weight in sarcoma-180 cells transplanted mice. 7. NSS prolonged significantly the survival time in sarcoma-180 cells transplanted mice.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5659-5665
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• 2014

Background: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro. Materials and Methods: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively. Results: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC): $2.25{\pm}0.02$ mmol trolox / mmol and $1.96{\pm}0.04$ mmol trolox / mmol respectively) and DPPH ($IC_{50}=3.75{\pm}0.04mg/mL$ and $IC_{50}=2.28{\pm}0.02mg/mL$ respectively). Both MTG and SRM demonstrate equal potency ($IC_{50}=25.20{\pm}1.53$ and $IC_{50}=22.19{\pm}1.06$ respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) ($IC_{50}24.40{\pm}1.26$). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration > $100{\mu}M$ towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60). Conclusions: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4671-4675
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• 2015

Moringa oleifera Lam. (Moringaceae) is widely consumed in tropical and subtropical regions for their valuable nutritional and medicinal characteristics. Recently, extensive research has been conducted on leaf extracts of M. oleifera to evaluate their potential cytotoxic effects. However, with the exception of antimicrobial and antioxidant activities, little information is present on the cytotoxic activity of the essential oil obtained from M. oleifera seeds. Therefore, the present investigation was designed to investigate the potential cytotoxic activity of seed essential oil obtained from M. oleifera on HeLa, HepG2, MCF-7, CACO-2 and L929 cell lines. The different cell lines were subjected to increasing oil concentrations ranging from 0.15 to 1 mg/mL for 24h, and the cytotoxicity was assessed using MTT assay. All treated cell lines showed a significant reduction in cell viability in response to the increasing oil concentration. Moreover, the reduction depended on the cell line as well as the oil concentration applied. Additionally, HeLa cells were the most affected cells followed by HepG2, MCF-7, L929 and CACO-2, where the percentages of cell toxicity recorded were 76.1, 65.1, 59.5, 57.0 and 49.7%, respectively. Furthermore, the $IC_{50}$ values obtained for MCF-7, HeLa and HepG2 cells were 226.1, 422.8 and $751.9{\mu}g/mL$, respectively. Conclusively, the present investigation provides preliminary results which suggest that seed essential oil from M. oleifera has potent cytotoxic activities against cancer cell lines.

• Molecules and Cells
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• 제37권6호
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• pp.457-466
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• 2014

Proteomic analysis is helpful in identifying cancerassociated proteins that are differentially expressed and fragmented that can be annotated as dysregulated networks and pathways during metastasis. To examine metastatic process in lung cancer, we performed a proteomics study by label-free quantitative analysis and N-terminal analysis in 2 human non-small-cell lung cancer cell lines with disparate metastatic potentials - NCI-H1703 (primary cell, stage I) and NCI-H1755 (metastatic cell, stage IV). We identified 2130 proteins, 1355 of which were common to both cell lines. In the label-free quantitative analysis, we used the NSAF normalization method, resulting in 242 differential expressed proteins. For the N-terminal proteome analysis, 325 N-terminal peptides, including 45 novel fragments, were identified in the 2 cell lines. Based on two proteomic analysis, 11 quantitatively expressed proteins and 8 N-terminal peptides were enriched for the focal adhesion pathway. Most proteins from the quantitative analysis were upregulated in metastatic cancer cells, whereas novel fragment of CRKL was detected only in primary cancer cells. This study increases our understanding of the NSCLC metastasis proteome.

• BMB Reports
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• 제39권4호
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• pp.448-451
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• 2006

Chemopreventive and cytotoxic effect of genistein against human breast cancer cell lines was investigated. Genistein inhibited cell proliferation in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. Cytochrome P450 (CYP) 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity was inhibited by genistein in a concentrationdependent manner. Genistein significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxy-genase-2 activity and protein expression at the concentrations of 10 (p < 0.05), 25 (p < 0.05) and 50 mM (p < 0.01). In addition, ornithine decarboxylase (ODC) activity was reduced to 53.8 % of the control after 6 h treatment with 50 mM genistein in MCF-7 breast cancer cells. These results suggest that genistein could be of therapeutic value in preventing human breast cancer.

• Journal of Microbiology and Biotechnology
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• 제11권5호
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• pp.876-879
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• 2001

${\gamma}$ -Tubulin is an essential component involved in microtubule nucleation. The present work examined whether the fast proliferation of cancer cells can be retarded by the depletion of ${\gamma}$ -tubulin expression. Two different gastric cancer cell lines and one control cell line were treated with antisence oligonucleotides complementary to the messenger RNA of ${\gamma}$ -tubulin. The$[^3H]$ -thymidine incorporation in the two gastric cancer cell lines, SNU-1 and SNU-216, was dramatically reducd by treatment with the ${\gamma}$ -tubulin antisense oligonucleotides in a dosage-dependent manner. In contrast, the control cell line, NIH/3T3, showed no significant effect from the antisense oligonucleotides even at a high concentration. The ablation of ${\gamma}$ -tubulin expression in the tumor cells resulted in an altered DNA synthesis during mitosis and it decreased the cell progression. Accordingly, the use of antisense oligonucleotides may be an effective way of inhibiting the proliferation of human gastric cancers.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권5호
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• pp.287-293
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• 2009

Cell survival is the result of a balance between programmed cell death and cellular proliferation. Cell membrane receptors and their associated signal transducing proteins control these processes. Of the numerous receptors and signaling proteins, epidermal growth factor receptor (EGFR) is one of the most important receptors involved in signaling pathways implicated in the proliferation and survival of cancer cells. EGFR is often highly expressed in human tumors including oral squamous cell carcinomas, and there is increasing evidence that high expression of EGFR is correlated with poor clinical outcome of common human cancers. Therefore, we examined the antiproliferative activity of gefitinib, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), in head and neck cancer cell lines. SCC-9, KB cells were cultured and growth inhibition activity of gefitinib was measured with MTT assay. To study influence of gefitinib in cell cycle, we performed cell cycle analysis with flow cytometry. Western blot was done to elucidate the expression of EGFR in cell lines and phosphorylation of EGFR and downstream kinase protein, Erk and Akt. Significant growth inhibition was observed in SCC-9 cells in contrast with KB cells. Also, flow cytometric analysis showed G1 phase arrest only in SCC-9 cells. In Western blot analysis for investigation of EGFR expression and downstream molecule phosphorylation, gefitinib suppressed phosphorylation of EGFR and downstream protein kinase Erk, Akt in SCC-9. However, in EGFR positive KB cells, weak expression of active form of Erk and Akt and no inhibitory activity of phosphorylation in Erk and Akt was observed. The antiproliferative activity of gefitinib was not correlated with EGFR expression and some possibility of phosphorylation of Erk and Akt as a predictive factor of gefitinib response was emerged. Further investigations on more reliable predictive factor indicating gefitinib response are awaited to be useful gefitinib treatment in head and neck cancer patients.

• 대한두경부종양학회지
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• 제27권2호
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• pp.190-197
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• 2011

Background and Objective : Radiation resistance(RR) is one of main determinants of treatment outcome in oral squamous cell carcinoma(OSCC), but accurate prediction of RR is difficult. We aim to establish RR OSCC cell lines and identify genes related with RR by a measurement of altered gene expression after inducing RR. Material and Methods : OSCC cell lines, SCC15, SCC25 and QLL1, were treated with 2Gy radiation per session, and parts of them were alive in finally accumulated dosage of 60Gy through 30 times repetition of radiotherapy for inducing RR cell lines. We compared results of cDNA array and proteomics in non-radiated cell lines and RR cell lines to detect changes of gene expression. Western blot was used for the validation of results. Results : cDNA array revealed 265 commonly up-regulated genes and 268 commonly down-regulated genes in 3 RR cell lines comparing their non-radiated counterpart. Among them, 30 cancer related genes were obtained. Proteomics showed 51 commonly altered protein expressions in 3 RR cell lines and 18 cancer related proteins were obtained. Among the detected genes, we found NM23-H1 and PA2G4 were over-expressed in both cDNA array and proteomics. Western blot showed increased expression of NME1 in RR cell lines but not in PA2G4. Conclusion: We concluded that NM23-H1 may be a candidate of RR related gene and over-expression of NM23-H1 could be a biomarker to predict RR in OSCC.

• Journal of Microbiology and Biotechnology
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• 제15권4호
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• pp.734-739
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• 2005

Myxobacterium sp. HK1, isolated from Korean soil, degrades cellulose, differentiates to fruiting body, and its 16s rDNA has $95\%$ similarity to Polyangium sp. An anticancer molecule, CDMHK, was identified from culture broth of Myxobacterium sp. HK1, and purified by Diaion HP20, Silica gel, Sephadex LH-20 chromatography, and preparative HPLC using an YMC OSD-A C18 column. The molecular structure and formula were determined to be $C_{l2}H_{l9}N_3O_2$ (M.W 237) by MS spectrometry, 300 MHz $^{1}H\;and\;^{13}C$ NMR. The CDMHK was not active against Escherichia coli, Staphylococcus aureus, and Candida albicans. However, this molecule inhibited the growth of various cancer cell lines. The $ED_{50}$ values of CDMHK were determined to be 0.147, 0.086, 0.18, 0.166, and 0.142 $\mu$g/ml against A549, SK-OV-3, SK-MEL-2, VF498, and HCTl5 cancer cell lines, respectively. In addition, the CDMHK was able to induce apoptosis of the CCRF-CEM cancer cell line, evidenced by DNA fragmentation assay and DAPI staining.