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Ginsenosides from the fruits of Panax ginseng and their cytotoxic effects on human cancer cell lines (인삼(Panax ginseng) 열매로부터 분리한 ginsenoside의 동정 및 암세포독성 효과)

  • Gwag, Jung Eun;Lee, Yeong-Geun;Hwang-Bo, Jeon;Kim, Hyoung-Geun;Oh, Seon Min;Lee, Dae Young;Baek, Nam-In
    • Journal of Applied Biological Chemistry
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    • v.61 no.4
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    • pp.371-377
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    • 2018
  • The fruits of Panax ginseng were extracted with 80% aqueous MeOH and the concentrates were partitioned into EtOAc, n-BuOH, and $H_2O$ fractions. The repeated $SiO_2$ and octadecyl $SiO_2$ column chromatographies for the EtOAc fraction led to isolation of five ginsenosides. The chemical structures of these compounds were determined as ginsenoside F1 (1), ginsenoside F2 (2), ginsenoside F3 (3), ginsenoside Ia (4), notoginsenoside Fe (5) based on spectroscopic analyses including nuclear magnetic resonance, MS, and infrared. Compounds 2-5 were isolated for the first time from the fruits of P. ginseng in this study. All isolated compounds were evaluated for cytotoxic activities against human cancer cell lines such as HCT-116, SK-OV-3, human cervix adenocarcinoma (HeLa), HepG2, and SK-MEL-5. Among them compounds 2, 4, and 5 showed significant cytotoxicity on cancer cells. Compound 2 exhibited cytotoxicity on SK-MEL-5, HepG2, and HeLa cells with $IC_{50}$ values of 82.8, 86.8, and $78.3{\mu}M$, respectively. Compound 4 showed cytotoxicity on HCT-116, SK-MEL-5, SK-OV-3, HepG2, and HeLa cells with $IC_{50}$ values of 24.5, 25.4, 26.3, 22.0, and $24.9{\mu}M$, respectively. Compound 5 did on SK-MEL-5 cell with $IC_{50}$ value of $81.7{\mu}M$. The cytotoxicity of ginsenoside 2, 4, and 5 isolated from the fruits of Panax ginseng showed strong inhibition effect against on cancer cells, all of which have a glucopyranosyl moiety on C-3.

Phytochemicals from Goniothalamus griffithii Induce Human Cancer Cell Apoptosis

  • Banjerdpongchai, Ratana;Khaw-on, Patompong;Pompimon, Wialrt
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3281-3287
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    • 2016
  • Bioactive compounds extracted from leaves and twigs of Goniothalamus griffithii include pinocembrin (PCN) and goniothalamin (GTN). The objectives of this study were to investigate the cytotoxic activities of PCN and GTN and their influence on molecular signaling for cell death in several human cancer cell lines compared to normal murine fibroblast NIH3T3 cells. GTN exhibited the most potent cytotoxicity against MCF-7 > HeLa > HepG2 > NIH3T3 cells with $IC_{50}$ values of 7.33, 14.8, 37.1 and $65.4{\mu}M$, respectively, whereas PCN was cytotoxic only to HepG2 cells with $IC_{50}$ values of ${\sim}80{\mu}M$. Apoptotic cell death was confirmed by staining the cells with annexin V-FITC and propidium iodide (PI) employing flow cytometry. Apoptosis was shown by externalization of phosphatidylserine in goniothalamin-treated MCF-7 cells in a dose response manner. Positive PI-stained cells with the typical morphology of apoptotic cells were increased dose-dependently. Furthermore, reduction of mitochondrial transmembrane potential was found in goniothalamin-treated MCF-7, HepG2 and HeLa cells. GTN treatment in MCF-7 increased caspase-3, -8 and -9 activities while GTN-induced HeLa cells showed an increase of both caspase-3 and -9 activities. But an increased caspase-8 activity was demonstrated in GTN- and PCN-treated MCF-7 and HepG2 cells, respectively. Taken together, GTN- and PCN-induced human cancer cell apoptosis was through different molecular mechanisms or signaling pathways, which might be due to different machineries in different types of cancer cells, as evidenced by the compound-modulated caspase activities in both intrinsic and/or extrinsic pathways.

The Cytotoxic effects of several Herbs against human cancer cell-lines (수종(數種)의 한약재(韓藥材)가 인체(人體) 암세포주(癌細胞柱)에 미치는 세포(細胞) 독성(毒性))

  • Jeong, Hyeon-U
    • The Journal of Internal Korean Medicine
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    • v.18 no.1
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    • pp.231-241
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    • 1997
  • The purpose of this research was to investigate effect of water extract of Euphorbiae Pekinensis Radix and Moutan Cortex Radicis on the proliferation of human cancer cell-lines. The effects of Euphorbiae Pekinensis Radix and Moutan Cortex Radicis on the proliferation of A431, HeLa, MOLT-4, K562 cells, Balb/c 3T3 cells, mouse thymocytes, splenocytes and human lymphocytes were estimated by MTT colorimetric assay. The results were as follows; 1. In proliferation of A431, HeLa, MOLT-4 and K562 cell-lines, Euphorbiae Pekinensis Radix and Moutan Cortex Radicis inhibited the proliferation of K562 cells. 2. In the combined effect of Euphorbiae Pekinensis Radix and mitomycin C, Moutan Cortex Radicis and mitomycin C, all herbs stimulated the proliferation of MOL T-4 cells. 3. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis did not inhibited the proliferation of Balb/c 3T3 cells. 4. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis stimulated the proliferation of mouse thymocytes. 5. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis stimulated the proliferation of mouse splenocytes. 6. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis stimulated the proliferation of human lymphocytes.

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Studies on the Chemical Nutagen-induced DNA Repair Synthesis in Relation to Chromosome Exchanges (突然變異誘發原에 의한 DNA回復合成과 染色體交換과의 聯關性에 관한 硏究)

  • Park, Sang-Dai;Um, Kyung-Il;Park, Kyung-Hee
    • The Korean Journal of Zoology
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    • v.19 no.4
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    • pp.179-186
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    • 1976
  • DNA repari synthesis and chromosome aberrations induced by various concentrations of alkylating agents (MMS, MNNG, MMC) in cultured human lymphocytes and HeLa $S_3$ cells were studied to determine the possibility of correlation between these two types of biological phenomena, and the results obtained were as follows: DNA repair synthesis was detected in MMC, MNNG and MMS treated HeLa $S_3$ cells at the concentrations of $3 \\times 10^{-7}M, 1 \\times 10^{-6}M, 5 \\times 10^{-4}M$, respectively. These results indicate that MMC is the most potent mutagen followed by MNNG, and MMS is the least potent among these three types of alkylating agents. MMC and MNNG did not show any significant increases of DNA repair synthesis as dose increased, while MMS did. Chromosome aberrations induced by MMC in human lymphocytes was increased as dose increased, but not chromosome exchanges. MNNG did not induce any significant amount of chromosome aberrations with doses, and exchanges were not observed in MNNG treated cells. MMS, however, induced both chromosome aberrations and exchanges, and their rates were increased as dose increased. These results suggest that DNA repair synthesis induced by these alklating agents may not be directly related to the production of chromosome aberrations and exchanges.

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Antiviral Activity of Hot-Water Extract and Its Ethanol Precipitate of Phellinus pini Fruiting Body (낙엽진흙버섯 자실체 유래 열수 추출물과 메탄을 침전물의 항바이러스활성)

  • Lee, Sae-Mi;Kim, Sung-Min;Lee, Yoon-Hee;Kim, Woo-Jung;Na, Ye-Seul;Kim, Hyun-Guell;Nam, Jae-Hwan;Shin, Hyun-Dong;Kwon, Doo-Han;Park, Yong-Il
    • Microbiology and Biotechnology Letters
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    • v.37 no.1
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    • pp.33-41
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    • 2009
  • The crushed fruiting body of Alaskan Porodaedalea pini (Brot.) Murrill (syn. Phellinus pini) was extracted in boiling water for 4 h with the yield of 20.5% in dry mass. This hot-water extract showed significant antiviral activity by inhibiting the plaque formation in HeLa cells by coxackievirus B3 (CVB3) and also showed highest inhibitory effect against neuraminidase activity among water extracts of various mushrooms. From the water extract, the ethanol precipitate (EP) and supernatant fraction (ES) were obtained through 75% ethanol precipitation with the yield of 43.3% and 28.3% in dry mass, respectively. Whereas ES did not show any detectable level of antiviral activity, EP showed significant dose-dependent inhibition of plaque formation by CVB3 in HeLa cells with an $EC_{50}$ (50% effective concentration) of 0.45 mg/mL. The cytotoxicity on HeLa cells by EP was relatively low with the $CC_{50}$ (50% cytotoxic concentration) of 2.25 mg/mL. EP also effectively inhibited neuraminidase activity in a dose-dependent manner showing up to 75% inhibition at 1.7 mg/mL. These results suggest that the hot-water extract and its EP of P. pini fruiting body can be a candidate for the development of a potent broad-range antiviral agent against influenza virus(Flu) as well as CVB3. The major active component of EP was shown to be a heteropolysaccharide-protein complex containing glucose as the main sugar residue with mole percentage of 79.8% and other sugars like galactose (19.2%), xylose (17%), mannose (5.8%), and fucose (4.6%) and a small portion (12.7%, in mass) of protein.

The Combined Effect of Moschus and Anti-tumor drug Mitomycin C (사향과 항암제 Mitomycin C의 병용효과)

  • Eun Jae Soon;Kim Dae Keun;Song Jung Mo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.6
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    • pp.1404-1408
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    • 2003
  • The combined effects of water-soluble fraction of Moschus (ME) and anti-tumor drug mitomycin C on the proliferation of human tumor cell-lines were estimated by MTT colorimetric assay. ME inhibited the proliferation of Hep G2, A540, HeLa, KHOS-NP and Balb/c 3T3 cells. Also, ME increased the cytotoxicity of mitomycin C on Hep G2, A549 and HeLa cells. In addition, ME enhanced the cell viability of murine splenocytes and human lymphocytes at the concentration of 100㎍/㎖. These results indicate that ME inhibits the proliferation of human tumor cells and increases the cytotoxicity of mitomycin C without cytoxicity on immune cells.

Detection of Anticancer Activity from the Root of Angelica gigas In Vitro

  • Ahn, Kyung-Seop;Sim, Woong-Seop;Kim, Ik-Hwan
    • Journal of Microbiology and Biotechnology
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    • v.5 no.2
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    • pp.105-109
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    • 1995
  • Anticancer activity of a fraction of the ethanol extract from the root of Korean angelica (Angelica gigas Nakai) was recognized in human cancer cell lines HeLa $S_3$, K-562, and Hep $G_2$. The extract blocked the phorbol ester-inducing megakaryocytic differentiation of K-562 cells, which indicated the modification of protein kinase C (PKC) activity. In vitro assay showed the activation of PKC by the extract. An effective fraction of the Angelica gigas extract, of which $R_f$ value was 0.64 in a thin layer chromatography, was a different component from those of European angelicas. The $ED_50$ value of the fraction was 8, 9, and $16\;\mu\textrm{m}/ml$ against HeLa $S_3\;Hep\;G_2$, and K-562 cells, respectively, while the fraction showed higher $ED_50$ values against normal cell lines.

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Thyroid Hormones Receptor/Reporter Gene Transcription Assay for Food Additives and Contaminants

  • Jeong Sang-Hee;Cho Joon-Hyoung
    • Toxicological Research
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    • v.21 no.4
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    • pp.333-338
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    • 2005
  • Many of thyroid hormones disrupting chemicals induce effects via interaction with thyroid hormone and retinoic acid receptors and responsive elements intrinsic in target cells. We studied thyroid hormones disrupting effects of food additives and contaminants including BHA, BHT, ethoxyquin, propionic acid, sorbic acid, benzoic acid, CPM, aflatoxin B1, cadmium chloride, genistein, TCDD, PCBs and TDBE in recombinant HeLa cells containing plasmid construct for thyroxin responsive elements. The limit of response of the recombinant cells to T3 and T4 was $1\times10^{-12}\;M$. BHA. genistein, cadmium and TBDE were interacted with thyroid receptors with dose-responsive pattern. In addition, BHA, BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, and TBDE showed synergism while cadmium chloride antagonism for T3-induced activity. This study elucidates that recombinant HeLa cell is sensitive and high-throughput system for the detection of chemicals that induce thyroid hormonal disruption via thyroid hormone receptors and responsive elements. Also this study raised suspect of BHA. BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, TBDE, genisteine and cadmium chloride as thyroid hormonal system disruptors.

Cytotoxicity of Daucus Carota L. on Various Cancer Cells (인체 암세포에 대한 당근 추출 성분의 세포독성효과)

  • 배송자;한은주;노승배
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.1
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    • pp.153-160
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    • 2000
  • We investigated the cytotoxic effects of roots and seeds Daucus carota L. on HepG2, HeLa, MCF7, SW626, C6 and NB41A3 cell lines by the MTT assay. Among extracts, the ethylacetate partition layer (DCMEA) of root of Daucus carota L. showed the strongest cytotoxic effects on HepG2, HeLa, C6 and NB41A3 cell lines. On the other hand, methanol(DCM), n-ethylacetate(DCMEA) and n-butanol(DCMB) extract of the seeds of Daucus carota L. also showed significant cytotoxic activities for all six cell lines. $\beta$-carotene, a well-known main component of Daucus carota L. was also tested for its cytotoxic effect. However, in all six cell lines, $\beta$-carotene falied to show significant cytotoxicity. Therefore, the anticancer effect of DCMEA of root fo Daucus carota L. and DCM, DCMH, DCMEA and DCMB extracts of seeds may be caused by components other than $\beta$-carotene. Futher studies are under way to isolate the compounds responsible for the significant cytotoxic activity.

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Study on the Antitumor Activity of Dichloromethane Extract of Tripterygium regelii SPRAGUE (뇌공등(雷公藤) 디클로메탄(CH$_2$Cl$_2$)분획의 항암효능 연구)

  • Park, Wan-Su
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.5
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    • pp.1196-1199
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    • 2006
  • Tripterygium regelii SPRAGUE is distributed in Korea and Northern China. This extract has been used as a herb medicine, especially antiparasitic, anti-inflammatory and detoxifying agent in East asia. During our research to develop new antitumor agents from natural products, Dichlorornethane (CH$_2$Cl$_2$) extract of Tripterygium regelii SPRAGUE (DTR) showed the potent apoptotic effects in A-549 lung cancer, HeLa-3 cervical cancer, SKMEL-2 melanoma cells in a dose-dependent manner. in order to purify major compounds from DTR, column chromatography was carried out gradually. Silica gel and RP-18 column chromatography for active fractions led to the isolation of a compound. The compound determined by 1 H-NMR was turned out to De Celastrol known to have antitumor activity.