• Title/Summary/Keyword: cancer cell lines

Search Result 1,724, Processing Time 0.041 seconds

Alternative Messenger RNA Splicing of Autophagic Gene Beclin 1 in Human B-cell Acute Lymphoblastic Leukemia Cells

  • Niu, Yu-Na;Liu, Qing-Qing;Zhang, Su-Ping;Yuan, Na;Cao, Yan;Cai, Jin-Yang;Lin, Wei-Wei;Xu, Fei;Wang, Zhi-Jian;Chen, Bo;Wang, Jian-Rong
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.5
    • /
    • pp.2153-2158
    • /
    • 2014
  • Beclin 1 is a key factor for initiation and regulation of autophagy, which is a cellular catabolic process involved in tumorigenesis. To investigate the role of alternative splicing of Beclin1 in the regulation of autophagy in leukemia cells, Beclin1 mRNA from 6 different types of cell lines and peripheral blood mononuclear cells from 2 healthy volunteers was reversely transcribed, subcloned, and screened for alternative splicing. New transcript variants were analyzed by DNA sequencing. A transcript variant of Beclin 1 gene carrying a deletion of exon 11, which encoded a C-terminal truncation of Beclin 1 isoform, was found. The alternative isoform was assessed by bioinformatics, immunoblotting and subcellular localization. The results showed that this variable transcript is generated by alternative 3' splicing, and its translational product displayed a reduced activity in induction of autophagy by starvation, indicating that the spliced isoform might function as a dominant negative modulator of autophagy. Our findings suggest that the alternative splicing of Beclin 1 might play important roles in leukemogenesis regulated by autophagy.

Effect on Antimutagenic and Cancer cell growth inhibition of Ixeris dentata Nakai (씀바귀의 항돌연변이성 및 암세포 성장억제효과)

  • Kim, Myong-Jo;Kim, Ju-Sung;Kang, Won-Hee;Jeong, Dong-Myong
    • Korean Journal of Medicinal Crop Science
    • /
    • v.10 no.2
    • /
    • pp.139-143
    • /
    • 2002
  • Ixeris dentate was used to extract the natural compounds with methanol and then the extracts were further fractionated using n-hexane, ethyl acetate, butanol and aqueous fraction. The methanol extract of Ixeris dentate had strong antimutagenic effect in Ames mutagenicity test. Among the extracts fractioned from the methanol extract, the butanol fraction exhibited the greatest antimutagenic effect suppressing the mutagenicity of Salmonella typhimurium TA100 with inhibition rate of 88.93%. Cancer cell lines include human lung carcinoma(A549), human breast adenocarcinoma(MCF-7) and human hepatocellular carcinoma(Hep3B). Hexane fraction showed the strongest effect against A549, MCF-7 and Hep3B at the same concentration compared to those of other fractions.

The Antiproliferative Effects of Compounds Isolated from Schisandra chinensis (오미자로부터 분리된 화합물의 암세포 증식 억제 효과)

  • Suh, Won-Se;Park, So Yeon;Min, Byung Sun;Kim, Sea Hyun;Song, Jeong Ho;Shim, Sang Hee
    • Korean Journal of Food Science and Technology
    • /
    • v.46 no.6
    • /
    • pp.665-670
    • /
    • 2014
  • We isolated twelve lignans and three terpenoids were isolated from the n-hexane fraction of Schisandra chinensis extract. Using spectroscopic data and comparison with available literature, the following compounds were identified: (1) wuweizisu C, (2) gomisin N, (3) deoxyschisandrin, (4) gomisin A, (5) schisandrin, (6) chamigrenal, (7) schisanlactone D, (8) methylgomisin O, (9) angeloylgomisin O, (10) (-)-gomisin $L_2$, (11) schisandronic acid, (12) (-)-gomisin $L_1$, (13) (+)-gomisin $K_3$, (14) gomisin J, and (15) tigloylgomisin H. Notably, this was the first finding that compound (8) was isolated from this plant. Each compound was evaluated for its in vitro cytotoxic activities toward HL-60 (human leukemia), HeLa (human cervical carcinoma), and MCF-7 (breast cancer) cell lines. Compounds (7), (8), and (9) exhibited strong cytotoxic effects on HL-60 ($IC_{50}$ 7.37, 6.60, and $8.00{\mu}M$, respectively), whereas compound (6) exhibited weak cytotoxicity towards MCF-7 ($IC_{50}$ $30.50{\mu}M$). In addition, compound (8) showed the strongest activity towards HeLa cells ($IC_{50}$ $1.46{\mu}M$).

Effects of Seaweeds on Matrix Metalloproteinases Derived from Normal Human Dermal Fibroblasts and Human Fibrosarcoma Cells (사람피부섬유아세포 및 섬유아육종세포로부터 유래된 기질금속단백질효소에 대한 해조류의 효능)

  • Park, In-Hwan;Lee, Sang-Hoon;Kim, Se-Kwon;Ngo, Dai-Nghiep;Jeon, You-Jin;Kim, Moon-Moo
    • Journal of Life Science
    • /
    • v.21 no.11
    • /
    • pp.1501-1510
    • /
    • 2011
  • In recent years novel potential pharmocological candidates have been looked for in animal, seaweed, sponge, fungi and marine bacteria resources. In this study, matrix metalloproteinases (MMPs) that play an important role in metastasis, arthritis, chronic inflammation and wrinkle formation were used as target enzymes to screen therapeutic agents. The inhibitory effects of several marine algae including green algae (5 species), red algae (18 species) and brown algae (4 species) methanolic extracts on MMPs were investigated in human dermal fibroblasts and human fibrosarcoma cell line (HT1080 cells) using gelatin zymography. In human dermal fibroblasts, the inhibition of MMP-2 was observed in Laurencia okamurae, Polysiphonia japonica, Grateloupia lanceolate and Sinkoraena lancifolia of red algae. In contrast, MMP-2 activation was enhanced in Enteromorpha compressa and E. linza of green algae, and Peltaronia bighamiae and Sargassum thunbergii of brown algae. In human fibrosarcoma cells, MMP-9 activation was decreased in the presence of S. thunbergii of brown algae, Polysiphonia japonica in red algae and E. compressa and E. linza of green algae. The interesting finding is that E. compressa and E. linza of green algae, and S. thunbergii of brown algae exhibited a positive effect on MMP-2 in normal cells, but a negative effect on MMP-9 in cancer cell lines. These results suggest that E. compressa and E. linza of green algae, and S. thunbergii of brown algae contain potential therapeutic ingredients for cancer treatment.

Antitumor Activity of 7-[2-(N-Isopropylamino)ethyl]-(20s)-camptothecin, CKD602, as a Potent DNA Topoisomerase I Inhibitor

  • Lee, Jun-Hee;Lee, Ju-Mong;Kim, Joon-Kyum;Ahn, Soon-Kil;Lee, Sang-Joon;Kim, Mie-Young;Jew, Sang-Sup;Park, Jae-Gab;Hong, Chung-Il
    • Archives of Pharmacal Research
    • /
    • v.21 no.5
    • /
    • pp.581-590
    • /
    • 1998
  • We developed a novel water-soluble camptothecin analobue, CKD602, and evaluated the inhibition of topoisomerase I and the antitumor activities against mammalian tumor cells and human tumor xenografts. CKD602 was a nanomolar inhibitor of the topoisomerase I enzyme in the cleavable complex assay. CKD602 was found to be 3 times and slightly more potent than topotecan and camptothecin as inhibitors of topoisomerase, respecitively. In tumor cell cytotoxicity, CKD602 was more potent than topotecan in 14 out of 26 human cancer cell lines tested, while it was comparable to camptothecin. CKD602 was tested for the in vivo antitumor activity against the human tumor xenograft models. CKD602 was able to imduce regression of established HT-29, WIDR and CX-1 colon tumors, LX-1 lung tumor, MX-1 breast tumor and SKOV-3 ovarian tumor as much as 80, 94, 76, 67, 87% and 88%, respectively, with comparable body weight changes to those of topotecan. Also the therapeutic margin (R/Emax: maximum tolerance dose/$ED-{58}$) of CKD602 was significantly higher than that of topotecan by 4 times. Efficacy was determined at the maximal tolerated dose levels using schedule dependent i.p. administration in mice bearing L1210 leukemia. On a Q4dx4 (every 4 day for 4 doses) schedule, the maximum tolerated dose (MTD) was 25 mg/kg per administration, which caused great weight loss and lethality in <5% tumor bearing mouse. this schedule brought significant increase in life span (ILS), 212%, with 33% of long-term survivals. The ex vivo antitumor activity of CKD602 was compared with that of topotecan and the mean antitumor index (ATI) values recorded for CKD602 were significantly higher than that noted for topotecan. From these results, CKD602 warrants further clinical investigations as a potent inhibitor of topoisomerase I.

  • PDF

GENE EXPRESSION PATTERNS INDUCED BY $TAXOL^{(R)}$ AND CYCLOSPORIN A IN ORAL SQUAMOUS CELL CARCINOMA CELL LINE USING CDNA MICROARRAY (cDNA Microarray를 이용한 구강편평세포암종 세포주에서 $Taxol^{(R)}$과 Cyclosporin A로 유도된 유전자 발현양상)

  • Kim, Yong-Kwan;Lee, Jae-Hoon;Kim, Chul-Hwan
    • Maxillofacial Plastic and Reconstructive Surgery
    • /
    • v.28 no.3
    • /
    • pp.202-212
    • /
    • 2006
  • It is well-known that paclitaxel($Taxol^{(R)}$), which is extracted from the pacific and English yew, has been used as a chemotherapeutic agent for ovarian carcinoma and advanced breast carcinoma and Cyclosporin A, which is highly lipophilic cyclic peptide and isolated from a fungus, has been also used as an useful immunosuppressive drug after transplantation and is associated with cellular apoptosis. Since 1953, in which James Watson, Rosalind Franklin and Francis Crick discovered the double helical structure of DNA, a few kinds of techniques for identifying gene expression have been developed. In postgenomic period, many of researchers have used the DNA microarray which is high throughput screening technique to screen large numbers of gene expression simultaneously. In this study, we searched and screened the gene expression in the oral squamous cell carcinoma cell lines treated with $Taxol^{(R)}$, cyclosporin or cyclosporin combined with $Taxol^{(R)}$ using cDNA microarray. The results were as following; 1. It was useful that the appropriate concentration of Cyclosporin A and $Taxol^{(R)}$ used in oral squamous cell carcinoma cell line was under 1${\mu}g/ml$ and 3${\mu}g/ml$. 2. In the experimental group in which $Taxol^{(R)}$ and $Taxol^{(R)}$ + Cyclosporin A were used, the cell growth was extremely decreased. 3. In the group in which Cyclosporin A was used, the MTT assay was rarely decreased which means the activity of succinyl dehydrogenase is remained in mitochondria but in the group in which the mixture of Cyclosporin A and $Taxol^{(R)}$ were used, the MTT assay was extremely decreased. 4. In the each group in which Cyclosporin A(3 ${\mu}g/ml$) and $Taxol^{(R)}$(1 ${\mu}g/ml$) were used, the cell arrest was appeared in $G_2/M$ phase and in the group in which $Taxol^{(R)}$(3 ${\mu}g/ml$) was used, the cell arrest was appeared in both S phase and $G_2/M$ phase. 5. In the oral squamous cell carcinoma cell line treated with $Taxol^{(R)}$, several genes including ANGPTL4, RALBP1 and TXNRD1, associated with apoptosis, SUI1, MAC30, RRAGA and CTGF, related with cell growth, HUS1 and DUSP5, related with cell cycle and proliferation, ATF4 and CEBPG, associated with transcription factor, BTG1 and VEGF, associated with angiogenesis, FDPS, FCER1G, GPA33 and EPHA4 associated with signal transduction and receptor activity and AKR1C2 and UGTA10 related with carcinogenesis were detected in increased levels. The genes that showed increaced expression in the oral squamous cell carcinoma cell line treated with Cyclosporin A were CYR61, SERPINB2, SSR3 and UPA3A which are known as genes associated with cell growth, carcinogenesis, receptor activity and transcription factor. The genes expressed in the HN22 cell line treated with cyclosporin combined with $taxol^{(R)}$ were ALCAM and GTSE1 associated with cancer invasiveness and cell cycle regulation.

MicroRNA Profile in the Helicobacter pylori-infected Gastric Epithelial Cells (Helicobacter pylori 감염 위상피세포에서 MicroRNA 발현 변화)

  • Chang Whan Kim;Sung Soo Kim;Tae Ho Kim;Woo Chul Chung;Jae Kwang Kim
    • Journal of Digestive Cancer Research
    • /
    • v.5 no.2
    • /
    • pp.105-112
    • /
    • 2017
  • Background: The expression of miRNAs in response to Helicobacter pylori infection has not been well explored. The aims of this study were to evaluate the H. pylori associated miRNAs in the gastric epithelial cells. Methods: We investigated gastric epithelial cell-line (HS3C) exposed H. pylori over 3 months and AGS cell-line (AGS) exposed H. pylori for 6 hour. After the extraction of miRNA from these cell-lines, microarray and real time PCR were performed to confirm the alteration of expression. Results: All 12 miRNAs chosen for real-time PCR are based on the result of microarray and their potential functions related to H. pylori infection. miR-21, miR-221, miR-222 were upregulated in the H. pylori infected AGS cell for 6 hours and HS3C cells. miR-99b, miR-200b, miR-203b and miR-373 were downregulated in the H. pylori infected AGS cell for 6 hours and HS3C cells. miR-23a, miR-23b, miR-125b, miR-141 and miR-155 were upregulated in HS3C cell line but not in H. pylori infected AGS cell for 6 hours. Conclusion: miR-21, miR-99b, miR-125b, miR-200b, miR-203b, miR-221, miR-222, and miR-373 are supposed to be related with oncogenesis of H. pylori infection. Further studies are needed for the evaluation of the function of these confirmed miRNAs.

  • PDF

Antimutagenic and Cytotoxicity Effects of Agaricus blazei Murill Extracts (아가리쿠스버섯(Agaricus blazei Murill) 추출물의 항돌연변이원성 및 세포독성 효과)

  • Ji, Jeong-Hwan;Kim, Mi-Nam;Choi, Kun-Pyo;Chung, Cha-Kwon;Ham, Seung-Shi
    • Korean Journal of Food Science and Technology
    • /
    • v.32 no.6
    • /
    • pp.1371-1378
    • /
    • 2000
  • This study was performed to determine the antimutagenic and cytotoxic effect of Agaricus blazei Murill methanol extract on Salmonella typhimurium TA98, TA100 and human cancer cell lines using Ames test and cytotoxicity assay, respectively. In Ames test, methanol extract from A. blazei Murill did not exhibit any mutagenicity and most of the samples showed high antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG), 4-nitroquinoline-1-oxide(4NQO), 3-amino-1,4-dimethyl-5H-pyrido [4,3-b] indol(Trp-P-1) and $benzo({\alpha})pyrene(B({\alpha})P)$. The methanol extracts of A. blazei Murill$(200\;{\mu}g/plate)$ showed approximately 92.4%, 81.9% and 83.4% inhibitory effect on the mutagenesis induced by 4NQO, Trp-P-1 and $B({\alpha})P$ against TA98 strain, whereas 87.3%, 94.7%. 92.3% and 89.9% inhibitions were observed on the mutagenesis induced by MNNG, 4NQO, Trp-P-1 and $B({\alpha})P$ against TA100 strain. The solvent fractions of methanol extracts from A. blazei Murill except water fraction showed high antimutagenic effects of $70{\sim}90%$ against mutation induced by MNNG, 4NQO. Trp-P-1 and $B({\alpha})P$. In anticancer effects of A. blazei Murill extract and fraction against cancer cell lines including human breast adenocarcinoma(MCF7), human lung carcinoma(A549), human fibrosarcoma(HT1080), human hepatocellular carcinoma(Hep3B), human epitheloid carcinoma(HeLa), human gastric carcinoma(KATO III) and human chronic myelogenous leukemia(K562) were investigated. The treatment of 1 mg/mL A. blazei Murill extracts had the highest cytotoxicity with 91.9% against HeLa, followed by KATO III(88.7%), A549(86.5%) and Hpe3B(84.3%). Whereas 1 mg/mL treatment of A. blazei Murill extracts had only $10{\sim}40%$ cytotoxicity on human normal liver cell (WRL68).

  • PDF

Study on the Safety of Firefly Luciferase in Human as a Transient Reporter Gene of Oncolytic Virotherapy (항암 바이러스 치료제의 보고유전자로써 반딧불이 루시퍼레이즈의 인체 내 안전성에 대한 연구)

  • Hong, Young Mi;Yoon, Woong Hee;Lee, You Ra;Kim, Soo Ji;Ngabire, Daniel;Narayanasamy, Badrinath;Ornella, Mefotse Saha Cyrelle;Kim, Myunghee;Cho, Euna;Lee, Bora;Hwang, Tae-Ho
    • Journal of Life Science
    • /
    • v.31 no.11
    • /
    • pp.1028-1036
    • /
    • 2021
  • Firefly luciferase (FLuc) can function as an efficient marker in the gene and viral therapies. Nonetheless, its clinical translation has been unaccomplished with the concerns on its exogenous nature and the similarity with human fatty acyl-CoA synthetase. In this study, we aimed to show safety of FLuc by conducting a set of preclinical experiments and a human use. Initially, FLuc permeability across the plasma membrane was investigated by delivering the FLuc-carrying viral vector, OTS-412, or the FLuc recombinant protein. After in vitro infection of OTS-412 into different cancer cell lines, FLuc activity was detected only in the cell lysates, but not in culture media. In addition, recombinant FLuc protein further showed the impermeability against the plasma membrane. Similar result was also observed in the in vivo experiment. After being injected into the VX2 tumor-bearing rabbit, the FLuc exclusively resided within the tumor tissue without being detected in the blood plasma or other organs. Human cancer cell lines originated from various organs were lysed and treated to the FLuc, and none of the human substrates was reactive against the FLuc. As a final step, FLuc recombinant protein was intravenously injected into a human. The luciferase was degraded with the half-life of 20 to 30 minutes in blood, and was untraceable from 1.5 hr after the injection. In addition, the blood plasma was nonresponsive against the fatty acids. Hematological analysis was also comparable between the pre- and post-injection. Altogether, our study collectively demonstrates the safety of the firefly luciferase.

Comparison of Immune Activities of Essential Oils from Juniperus rigida S. et Z. and Boswellia carteii Birew by Supercritical Fluid Extraction System (노간주나무와 유향나무의 초임계 공법으로 추출한 정유의 면역 활성 비교)

  • Mun, Hyoung-Chul;Park, Jin-Hong;Kim, Dae-Ho;Yoo, Jae-Eun;Kim, Jung-Hwa;Kim, Chang-Ho;Kim, Jong-Dai;Park, Young-Sik;Lee, Hak-Ju;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
    • /
    • v.12 no.3
    • /
    • pp.243-248
    • /
    • 2004
  • Essential oils from Needl Juniperrus seed and trunk (Juniperrus rigida Sieb.) and Olibanum resin (Boswellia carteii Birew) were extracted by a supercritical fluid extraction system (SFE) and immune activity of each essential oils were observed. The immune activities of each essential oil were compared. Essential oil from Olibanum resin enhanced the growth of human immune T cell up to 1.33 times, compared to control group. Each essential oils showed the potent inhibitory effect on the human cancer cell lines, and increased the secretion of cytokines, IL-6 and $TNF-{\alpha}$ from human B cell as well as the growth of human immune cells.