• Title/Summary/Keyword: A549 Cell

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Purification and Characterization of CDMHK, a Growth Inhibitory Molecule Against Cancer Cell Lines, from Myxobacterium sp. HK1 Isolated from Korean Soil

  • LEE HAN-KI;LEE IN-HYE;YIM JEE-SUN;KIM YONG-HO;LEE SANG-HEE;LEE KISAY;KOO YOON-MO;KIM SANG-JIN;JEONG BYEONG-CHUL
    • Journal of Microbiology and Biotechnology
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    • v.15 no.4
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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.

Anti-proliferative Effects of Traditional Korean Doenjang across Different Aging Periods on Cancer Cell Lines (숙성기간으로 구분된 전통된장의 암세포 증식억제 효과)

  • Yang, Hye Jeong;Hur, Jinyoung;Hong, Sang Pil
    • Journal of the Korean Society of Food Culture
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    • v.35 no.5
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    • pp.467-477
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    • 2020
  • Doenjang is a major fermented soy-based food in Korea. Recent investigations have shown that fermented soybean foods have immunity-enhancing, anti-cancer, anti-obesity and anti-diabetic effects. Several studies also have reported that genistein and daidzein, which are easily absorbed in the body are produced in larger quantities in aged doenjang. The purpose of this study was to evaluate the variations in the anti-cancer effects of commercialized doenjang as it ages. Four groups were formed for this study according to aging periods of doenjang, namely short (under 5 years, S group), mid (under 10 years, M group), long (under 15 years, L group) and very long (over 15 years, E group). The anti-cancer effects of doenjang were determined by cell cytotoxicity assays in A549, YAC-1, and HepG2 cancer cell lines. Also, NK cell activity and splenocyte proliferation were assayed for cancer immunotherapy. The quantities of phenolic compounds in doenjang at different ages were also measured. The results showed that the anti-cancer effects increased in the S and M groups for all three cancer cell lines. Interestingly, similar to this result, splenocyte proliferation and NK activity were also the highest in the S and M groups. In contrast, the E group showed significantly reduced splenocyte proliferation. The quantity of phenolic compounds was similar to that of the anti-cancer results. Collectively, these results suggest that the fermentation period of doenjang plays a very important role in determining its anti-cancer effects.

Red blood cell distribution width is useful in discriminating adult onset Still's disease and sepsis within 24 hours after hospitalization

  • Park, Hee-Jin;Song, Jungsik;Park, Yong-Beom;Lee, Soo-Kon;Lee, Sang-Won
    • The Korean journal of internal medicine
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    • v.33 no.6
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    • pp.1234-1240
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    • 2018
  • Background/Aims: Red blood cell distribution width (RDW) is a value representing the heterogeneity in the size of red blood cell, and it is usually used in distinguishing types of anaemia. Recently, it was reported that it could reflect the burden of inflammation in diverse diseases and their prognosis. Hence, in this study, we investigated whether RDW may contribute to discriminating adult onset Still's disease (AOSD) from sepsis in serious febrile patients within 24 hours after hospitalization. Methods: We reviewed the medical records and enrolled 21 AOSD patients, 27 sepsis patients and 30 matched healthy controls. We collected at least two laboratory results of variables including RDW within 24 hours after hospitalization, and we calculated their mean values. Results: Sepsis patients showed the significantly increased median white blood cell count, compared to AOSD patients ($14,390.0/mm^3$ vs. $12,390.0/mm^3$, p = 0.010). The median RDW in sepsis patients was higher than that in AOSD patients (15.0% vs. 13.3%, p = 0.001), and furthermore, the median RDW in both patient-groups was significantly higher than that in healthy controls. In contrast, the median ferritin level in sepsis patients was lower than that in AOSD patients (544.0 mg/dL vs. 3,756.6 mg/dL, p = 0.001). In multivariate analysis, RDW ${\geq}14.8%$ (odds ratio, 17.549) and ferritin < 2,251.0 mg/dL (odds ratio, 32.414) independently suggested sepsis more than AOSD in patients initially presenting with fever requiring hospitalization. Conclusions: RDW might be a rapid and helpful marker for a differential diagnosis between AOSD from sepsis at an early phase.

HY253, a Novel Decahydrofluorene Analog, Induces Apoptosis via Intrinsic Pathway and Cell Cycle Arrest in Liver Cancer HepG2 Cells

  • Choi, Ko-woon;Suh, Hyewon;Jang, Seunghun;Kim, Dongsik;Lee, Chul-Hoon
    • Journal of Microbiology and Biotechnology
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    • v.25 no.3
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    • pp.413-417
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    • 2015
  • Recently, we isolated HY253, a novel decahydrofluorene analog with a molecular structure of 7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol from the roots of Aralia continentalis, which is known as Dokwhal (獨活), a traditional medicinal herb. Moreover, we previously reported its cytotoxic activity on cancer cell proliferation in human lung cancer A549 and cervical cancer HeLa cells. The current study aimed to evaluate its detailed molecular mechanisms in cell cycle arrest and apoptotic induction in human hepatocellular carcinoma HepG2 cells. Flow cytometric analysis of HepG2 cells treated with $60{\mu}M$ HY253 revealed appreciable cell cycle arrest at the G1 phase via inhibition of Rb phosphorylation and down-regulation of cyclin D1. Furthermore, using western blots, we found that up-regulation of cyclin-dependent kinase inhibitors, such as p21CIP1 and p27KIP1, was associated with this G1 phase arrest. Moreover, TUNEL assay and immunoblottings revealed apoptotic induction in HepG2 cells treated with $60{\mu}M$ HY253 for 24 h, which is associated with cytochrome c release from mitochondria, via down-regulation of anti-apoptotic Bcl-2 protein, which in turn resulted in activation of caspase-9 and -3, and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Accordingly, we suggest that HY253 may be a potent chemotherapeutic hit compound for treating human liver cancer cells via up-regulation and activation of the p53 gene.

Importance of Sulfonylimidazolidinone Motif of 4-Phenyl-1-arylsulfonylimidazolidinones for Their Cytotoxicity: Synthesis of 2-Benzoyl-4-phenyl[1,2,5]thiazolidine-1,1-dioxides and Their Cytotoxcity

  • Kim, Il-Whan;Lee, Chong-Kyo;Kim, Hae-Soo;Jung, Sang-Hun
    • Archives of Pharmacal Research
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    • v.26 no.1
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    • pp.9-14
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    • 2003
  • For probing the importance of planarity of imidazolidinone motif of 4-phenyl-1-(benzenesulfonyl)imidazolidinones 1 for their cytotoxicity, 4-phenyl-2-(benzoyl)[1,2,5]thiadiazolidine-1,1-dioxide (2a), 4-phenyl-2-(p-toluoyl)[1,2,5]thiadiazolidine-1,1-dioxide (2b), 4-phenyl-2-(phenylcarbamoyl)[1,2,5]thiadiazolidine-1,1-dioxide (3a), and 4-phenyl-2-(p-tolylcarbamoyl)[1,2,5]thiadiazolidine-1,1-dioxide (3b) were prepared along with their regioisomers (5a, 5b, 9a, 9b) and their cytotoxicity were measured against human lung carcinoma (A549), human colon carcinoma (COLO205), human ovarian cancer (SK-OV-3), human leukemic cancer (K562), and murine colon adenocarcinoma (Colon26) cell lines in vitro. All compounds prepared do not show any activity against all five cancer cell lines unlike 1. Compounds 1 possess planarity of imidazolidinone, especially in sulfonylurea moiety ($-SO_2$NHCONH-). However compounds 2 and 3 have nonplanar 5-membered ring, [1,2,5]thiadiazolidine-1,1-dioxides. Such structural differentiation might result in the loss of activity. Therefore the inactivity of 2 and 3 could also be an indication for the necessity of planarity of imidazolidinone ring of 1 for their cytotoxic activity.

Comparison of Anticancer and Immuno-Modulatory Activities in the different parts of the Acer mono Max. and Acer okamotoanum (고로쇠와 우산고로쇠 나무의 부위별 항암 및 면역조절능 비교)

  • Qadir, Syed Abdul;Kim, Cheol-Hee;Kwon, Min-Chul;Lee, Hak-Ju;Kang, Ha-Young;Choi, Don-Ha;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.15 no.6
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    • pp.405-410
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    • 2007
  • This study was performed to investigate anticancer activities and immuno modulatory activities in the several parts of the A. mono and A. okamotoanum. The cytotoxicity of 1 $mg/m{\ell}$ of the water extracts on normal human lung cell(HEL299) was < 19.5%. The anticancer activity of all extracts were increased in over 55% against AGS (stomach adenocarcinoma), A549 (lung adenocarcinoma), Hep3B (liver adenocarcinoma, and MCF-7 (breast adenocarcinoma) cells. The growth of human immune B and T cells was improved of A. mono and A. okamotoanum in adding 1.0 $mg/m{\ell}$ concentration. The secretion of the IL-6 and $TNF-{\alpha}$ of human immune B and T cells was increased with all extracts of A. mono and A. okamotoanum. All extracts of. A. mono and A. okamotoanum increased NK cell growth. The results showed that the barks and woods extracts of A. mono and A. okamotoanum had useful biological activities. In addition, bark of A. okamotoanuim showed the highest anticancer and immune activities.

Analysis of 5-aza-2'-deoxycytidine-induced Gene Expression in Lung Cancer Cell Lines (폐암 세포주에서 5-aza-2'-deoxycytidine 처치에 의해 발현되는 암항원 유전자 분석)

  • 김창수;이해영;김종인;장희경;박종욱;조성래
    • Journal of Chest Surgery
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    • v.37 no.12
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    • pp.967-977
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    • 2004
  • Background: DNA methylation is one of the important gene expression mechanisms of the cell. When cytosine of CpG dinucleotide in promotor is hypomethylated, expression of some genes that is controlled by this promoter is altered. In this study, the author investigated the effect of DNA demethylating agent, 5-aza-2'-deoxycytidine (ADC), on the expressions of cancer antigen genes, MHC and B7 in 4 lung cancer cell lines, NCIH1703, NCIH522, MRC-5, and A549. Material and Method: After treatment of cell lines, NCIH1703, NCIH522, MRC-5 and A549 with ADC (1 uM) for 48 hours, RT-PCR was performed by using the primers of MAGE, GAGE, NY-ESO-1, PSMA, CEA, and SCC antigen gene. In order to find the optimal ADC treatment condition for induction of cancer antigen, we studied the effect of ADC treatment time and dose on the cancer antigen gene expression. To know the effect of ADC on the expression of MHC or B7 and cell growth, cells were treated with 1 uM of ADC for 72 hours for FACS analysis or cells were treated with 0.2, 1 or 5 uM of ADC for 96 hours for cell counting. Result: After treatment of ADC (1 uM) for 48 hours, the expressions of MAGE, GAGE, NY-ESO-1, and PSMA genes increased in some cell lines. Among 6 MAGE isotypes tested, and gene expression of MAGE-1, -2, -3, -4 and -6 could be induced by ADC treatment. However, CEA gene expression did not change and SCC gene expression was decreased by ADC treatment. Gene expression was generally induced 24 - 28 hours after ADC treatment and expression of MAGE, GAGE, and NY-ESO-1 was maintained at least 14 days after ADC ADC teatment, and expression of MAGE, GAGE, and NY-ESO-1 was maintained at least 14 days after ADC teatment in ADC-Free medium. Most gene expression could be induced at 0.2 uM of ADC, but gene expression increased dependently on ADC treatment dose. The expression of MHC and B7 was not increased by ADC treatment in all four cell lines, and the growth rate of 4 cell lines decreased significantly with the increase of ADC concentrations. Conclusion: Treatment of lung cancer cell lines with ADC increases the gene expression MAGE, GAGE and NY-ESO-1 that are capable of induction of cytotoxic T lymphocyte response. We suggest that treatment with 1 uM of ADC for 48 hours and then culturing in ADC-free medium is optimal condition for induction of cancer antigen. However, ADC has no effect on MHC and B7 induction, additional modification for increase of expression of MHC, B7 and cytokine will be needed for production of efficient cancer cell vaccine.

In Vitro Antitumor Properties of an Isolate from Leaves of Cassia alata L

  • Olarte, Elizabeth Iglesias;Herrera, Annabelle Aliga;Villasenor, Irene Manese;Jacinto, Sonia Donaldo
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3191-3196
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    • 2013
  • Leaf extracts of Cassia alata L (akapulko), traditionally used for treatment of a variety of diseases, were evaluated for their potential antitumor properties in vitro. MTT assays were used to examine the cytotoxic effects of crude extracts on five human cancer cell lines, namely MCF-7, derived from a breast carcinoma, SK-BR-3, another breast carcinoma, T24 a bladder carcinoma, Col 2, a colorectal carcinoma, and A549, a nonsmall cell lung adenocarcinoma. Hexane extracts showed remarkable cytotoxicity against MCF-7, T24, and Col 2 in a dose-dependent manner. This observation was confirmed by morphological investigation using light microscopy. Further bioassay-directed fractionation of the cytotoxic extract led to the isolation of a TLC-pure isolate labeled as f6l. Isolate f6l was further evaluated using MTT assay and morphological and biochemical investigations, which likewise showed selectivity to MCF-7, T24, and Col 2 cells with $IC_{50}$ values of 16, 17, and 17 ${\mu}g/ml$, respectively. Isolate f6l, however, showed no cytotoxicity towards the non-cancer Chinese hamster ovarian cell line (CHO-AA8). Cytochemical investigation using DAPI staining and biochemical investigation using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-a method used to detect DNA fragmentation-together with caspase assay, demonstrated apoptotic cell death. Spectral characterization of isolate f6l revealed that it contained polyunsaturated fatty acid esters. Considering the cytotoxicity profile and its mode of action, f6l might represent a new promising compound with potential for development as an anticancer drug with low or no toxicity to non-cancer cells used in this study.

Trichodermamide A and Aspergillazine A, Two Cytotoxic Modified Dipeptides from a Marine-Derived Fungus Spicaria elegans

  • Liu Rui;Gu Qian-Qun;Zhu Wei-Ming;Cui Cheng-Bin;Fan Guo-Tao
    • Archives of Pharmacal Research
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    • v.28 no.9
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    • pp.1042-1046
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    • 2005
  • Two known modified dipeptides, trichodermamide A (1) and aspergillazine A (2), were isolated from an ethyl acetate extract of the metabolite of a marine-derived fungus Spicaria elegans, and were found to have a weak cytotoxic effect on three cancer cell lines P388, A-549, and HL-60 agreed. To our knowledge, this is the first report on the isolation of compounds 1 and 2 from the fungus Spicaria elegans and their cytotoxic effect.

Cancer Cell Growth Inhibition of Lanostane-type Triterpenoids Isolated from Ganoderma gibbosum (칠황버섯으로부터 분리한 Lanostane-type Triterpenoid의 암세포성장 억제효과)

  • Kim, Donghwa;Lee, Sang Kook;Park, Hee-Juhn
    • Korean Journal of Pharmacognosy
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    • v.51 no.1
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    • pp.36-40
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    • 2020
  • The CHCl3 fraction of the MeOH extract of Ganoderma gibbosum (Ganodermataceae) exhibited cytotoxic activity on five cancer cell lines (MDA-MB-231, SK-hep1, A549, HCT116, and SNU638). Six highly oxygenated lanostane-type triterpenoids (lanostanoids) were isolated by column chromatography to test cytotoxicity on cancer cells. The five known lanostanoids were identified as gibbosic acids A, B, D, G, and H by comparison of molecular ion peaks with the literature data. The structure of a new lanostanoid, gibbosic acids I, was identified to be 3β,8β,15β,20S-tetrahydroxy-7,12,23-trioxolanost-9(11)-en-26-oic acid on the basis of NMR and MS spectroscopy. The three lanostanoids of gibbosic acids A, H, and I of the six isolates significantly suppressed the growth of cancer cells. In particular, the IC50 of gibbosic acid H was prominently low ranging from 2.64-6.56 μM.