• Title/Summary/Keyword: Cytotoxicities

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New hydroperoxylated and 20,24-epoxylated dammarane triterpenes from the rot roots of Panax notoginseng

  • Shang, Jia-Huan;Sun, Wen-Jie;Zhu, Hong-Tao;Wang, Dong;Yang, Chong-Ren;Zhang, Ying-Jun
    • Journal of Ginseng Research
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    • v.44 no.3
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    • pp.405-412
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    • 2020
  • Background: Root rot is a serious destructive disease of Panax notoginseng, a famous cultivated araliaceous herb called Sanqi or Tianqi in Southwest China. Methods: The chemical substances of Sanqi rot roots were explored by chromatographic techniques. MS, 1D/2D-NMR, and single crystal X-ray diffraction were applied to determine the structures. Murine macrophage RAW264.7 and five human cancer cell lines were used separately for evaluating the antiinflammatory and cytotoxic activities. Results and Conclusion: Thirty dammarane-type triterpenes and saponins were isolated from the rot roots of P. notoginseng. Among them, seven triterpenes, namely, 20(S)-dammar-25-ene-24(S)-hydroperoxyl-3β,6α,12β,20-tetrol (1), 20(S)-dammar-3-oxo-23-ene-25-hydroperoxyl-6α,12β,20-triol (2), 20(S)-dammar-12-oxo-23-ene-25-hydroperoxyl-3β,6α,20-triol (3), 20(S)-dammar-3-oxo-23-ene-25-hydroperoxyl-12β,20-diol (4), 20(S),24(R)-epoxy-3,4-seco-dammar-25-hydroxy-12-one-3-oic acid (5), 20(S),24(R)-epoxy-3,4-seco-dammar-25-hydroxy-12-one-3-oic acid methyl ester (6), and 6α-hydroxy-22,23,24,25,26,27-hexanordammar-3,12,20-trione (7), are new compounds. In addition, 12 known ones (12-16 and 19-25) were reported in Sanqi for the first time. The new Compound 1 showed comparable antiinflammatory activity on inhibition of NO production to the positive control, whereas the known compounds 9, 12, 13, and 16 displayed moderate cytotoxicities against five human cancer cell lines. The results will provide scientific basis for understanding the chemical constituents of Sanqi rot roots and new candidates for searching antiinflammatory and antitumor agents.

Antioxidative, Antimutagenic and Cytotoxic Effects of the Mineral Water (광천수의 항산화성, 항돌연변이원성 및 세포독성 효과)

  • Ham Seung-shi;Kim Soo-hyun;Moon Seon-young;Jeon Mi-Sun;Oh Deog-Hwan;Cui Cheng-Bi
    • Journal of Food Hygiene and Safety
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    • v.20 no.1
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    • pp.53-57
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    • 2005
  • This study was performed to observe the components, antioxidative, antimutagenic and cytotoxic effects of the mineral water using AOAC method, DPPH free radical donating method, Ames test and SRB assay. Mineral water contained eleven kinds of minerals among the total seventeen components and sodium and potassium ion were main components. Mineral water showed electron donating activities ($175.9{\mu}g$). The inhibition rate of mineral water ($200{\mu}g/plate$) in the Sallmonella typhimurium TA98 strain showed $54\%$ against the mutagenesis induced by Trp-P-1. In addition, same concentration of mineral water the Sallmonella typhimurium TA100 strain showed highest $67\%,\;65.8\%\;and\;63\%$ inhibition against $B({\alpha})P$, 4NQO and Trp-P-1, respectively. The cytotoxic effects of mineral water against the cell lines with Human lung carcinoma (A549), Human breast adenocarcinoma (MCF-7), Human stomach adenocarcinoma (AGS) and Human cervical adenocarcinoma (Hela) were inhibited with the increase of the mineral water. The treatment of $50{\mu}g/well$ of mineral water showed cytotoxicities of $66\%,\;47.6\%,\;37.7\%\;and\;45.6\%$ against A549, MCF-7, AGS and Hela.

The Anticancer Mechanisms of Taxol-Diethylenetriamine pentaacetate Conjugate in HT29 Human Colorectal Cancer cells

  • Lee, Na-Kyung;Kim, Hyun-Jeong;Yang, Seung-Ju;Kim, Yoon-Suk;Choi, Hyun-Il;Shim, Moon-Jeong;Awh, Ok-Doo;Kim, Tae-Ue
    • BMB Reports
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    • v.34 no.3
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    • pp.237-243
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    • 2001
  • Taxol, a natural product extracted from the Taxus brevifolia, is known to have significant anti-tumor activities against many common cancers, including ovarian and breast cancers. Despite the pronounced anti-tumor activity of this compound, its poor solubility in aqueous solutions hampers its clinical applications. We studied the anticancer mechanisms of the water-soluble taxol diethylenetriamine pentaacetate (DTPA) used for radiolabeling, and compared it to that of taxol. In vitro cytotoxicities of taxol and taxol-DTPA conjugate were tested in HT29 human colorectal cancer cells by the MTT method. As the result, the $IC_{50}$ value of the taxol-DTPA conjugate was about three fold higher than that of taxol. When analyzed by an agarose gel electrophoresis, the DNA ladders became evident after the incubation of cells with the taxol-DTPA conjugate for 24 h. We also found morphological changes of the cells undergoing apoptosis with electron microscopy Next, we examined the signal pathway of taxol-DTPA conjugate-induced apoptosis in HT29 cells. The activation of extracellular signal-regulated protein kinase (ERK1/2) occurred at 10, 30, 60 and 120 min after 200 nM taxol-DTPA conjugate treatment. The pretreatment of the MEK inhibitor (PD98059) completely blocked the taxol-DTPA conjugate-induced ERK1/2 activation. The activated ERK1/2 translocated into the nucleus at the same time and phosphorylated its transcriptional factor, c-Jun. These results suggest that the taxol-DTPA conjugate has an apoptotic activity in HT29 cells, and that its proapoptic activity might be related with the signal transduction via ERK1/2 and c-Jun similar to that of taxol.

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Effect of Wood Vinegar Produced from Morus alba on Hypersecretion of Airway Mucus (상지(桑枝) 목초액이 호흡기 객담 과다분비에 미치는 영향)

  • Kim, Ho;Jung, Hye-Mi;Kim, Sol-Li;Seo, Un-Kyo
    • The Journal of Internal Korean Medicine
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    • v.31 no.3
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    • pp.650-666
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    • 2010
  • Objectives : In this study, the author tried to investigate whether wood vinegar produced from Morus alba (MA) significantly affects the increase in airway epithelial mucosubstances and hyperplasia of tracheal goblet cells of rats, and in vitro airway mucin secretion and PMA- or EGF- or TNF-alpha-induced MUC5AC mucin production / gene expression from human airway epithelial cells. Materials and Methods : For the in vivo experiment, the author induced hypersecretion of airway mucus and goblet cell hyperplasia by exposure of rats to SO2 over 3 weeks. Effect of orally-administered MA over 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats and hyperplasia of goblet cells were assessed using histopathological analysis after staining the epithelial tissue with alcian blue. For the in vitro experiment, confluent RTSE cells were chased for 30 min in the presence of MA to assess the effect of MA on mucin secretion by enzyme-linked immunosorbent assay (ELISA). Also, effects of MA on PMA- or EGF- or TNF-alpha-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of MA and treated with PMA (10 ng/ml), EGF (25 ng/ml) or TNF-alpha (0.2 nm) for 24 hrs, to assess both effects of MA on PMA- or EGF- or TNF-alpha-induced MUC5AC mucin production by enzyme-linked immunosorbent assay (ELISA) and gene expression by reverse transcription-polymerase chain reaction (RT-PCR). Possible cytotoxicities of MA in vitro were assessed by examining LDH release from RTSE cells and the rate of survival and proliferation of NCI-H292 cells. In vivo liver and kidney toxicities of MA were evaluated by measuring serum GOT/GPT activities and serum BUN/creatinine concentrations of rats after administering MA orally. Results : 1. MA decreased the amount of intraepithelial mucosubstances of rats exposed to sulfur dioxide inhalationally. 2. MA decreased in vitro mucin secretion from cultured RTSE cells. 3. MA significantly inhibited PMA-, EGF-, and TNF-alpha-induced MUC5AC mucin productions and the expression levels of MUC5AC mRNA from NCI-H292 cells. 4. MA did not show either in vitro or in vivo hepatic or renal toxicities. Conclusion : The results from this study suggests that MA can regulate the secretion, production and gene expression of airway mucin observed in diverse respiratory diseases accompanied by mucus hypersecretion and does not show in vivo toxicity to liver and kidney functions after oral administration. Effects of MA should be further studied using animal experimental models that simulate the diverse pathophysiology of respiratory diseases via future research.

Biological Activities of Seven Melania Snails in Korea (국내산 7종 다슬기 추출물의 생리활성 특성 비교)

  • Kim, Yeon-Kye;Moon, Ho-Sung;Lee, Moon-Hee;Park, Mi-Ju;Lim, Chi-Won;Park, Hee-Yeon;Park, Jin-Il;Yoon, Ho-Dong;Kim, Dae-Hee
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.42 no.5
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    • pp.434-441
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    • 2009
  • This study was conducted to compare the biological activities of 7 melania snails from the family Pleuroceridae (Semisulcospira coreana, Koreanomelania nodifila, Semisulcospira forticosta, Koreoleptoxis globus ovalis, Semisulcospira libertina, Semisulcospira tegulata and Semisulcospira gottschei) in Korea. Among the 7 species, S. coreana, Korean. nodifila, S. forticosta and S. gottschei showed over 80% cytotoxicities on three cancer cell lines (SNU-1, A549 and Hep 3B) compared to the non-treatment, whereas S. libertina and S. tegulata showed almost no growth inhibition activities on the same cancer cell lines. In relation to ACE inhibition activity, only S. coreana, Korean. nodifila, and S. forticosta showed over 60% ACE inhibition activities, whereas other melania snails exhibited inhibition activities of lower than 25%. DPPH radical scavenging activities were also determined, and used to categories melania snails into three groups based on Duncan's multiple range test at P<0.05. The amount of TNF-${\alpha}$ produced by in vitro mouse peritoneal macrophage was determined according to bioactivity on L-929 cells. Three melania snails, S. coreana, Korean. nodifila and S. gottschei, exhibited 95.2%, 89.7% and 93.7% cell death(%) on L-929 cells, respectively. Glucose-6-phosphate dehydrogenase inhibitory activity was also obtained in the extract of S. coreana (31.9%) and Korean. nodifila (28.1%), showing that these extracts can be used as supplemental dietary health foods. In conclusion, we believe that the extracts of melania snails should be given due consideration in functional health food development.

Cytotoxicities of Tumor-specific T Lymphocytes Primed by Glioma Apoptotic Body - or Glioma Cell Lysate-pulsed Dendritic Cells

  • Kim, Jong-Tae;Chung, Dong-Sup;Kwak, Seung-Won;Han, Young-Min;Park, Young-Sup;Kim, Moon-Chan
    • Journal of Korean Neurosurgical Society
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    • v.38 no.2
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    • pp.126-131
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    • 2005
  • Objective : The choice of tumor antigen for dendritic cell[DC]-loading has still been an unresolved problem in the DC-based vaccine strategies against malignant gliomas that has not been found well-characterized tumor specific antigens. In this study, we compare tumor-specific T cell response induced by glioma apoptotic body[GAB]-pulsed DCs to response induced by glioma cell lysate-pulsed ones quantitatively. Methods : DCs generated in the presence of granulocyte macrophage-colony stimulating factor and interleukin[IL]-4 from peripheral blood mononuclear cells[PBMCs] of HLA-A2 positive healthy donors were cultured. Each GABs and glioma cell lysate generated from HLA-A2 positive T98G glioblastoma cells were co-incubated with DCs. $CD8^+$ T lymphocytes isolated from PBMCs of same donors were cultured in media containing IL-2 and either stimulated by GAB- or lysate-pulsed DCs three times at a weekly interval. The interferon[IFN]-${\gamma}$ concentrations of each cell culture supernate were measured by enzyme immunoassay technique. Cytolytic activity of the generated cytotoxic $CD8^+$ T cells either stimulated with GAB- or lysate-pulsed DCs was determined by a standard 4-h $^{51}Cr$-release assay. Results : IFN-${\gamma}$ production and cytolytic activity of effector T cells stimulated by GAB-pulsed DCs were significantly higher than those of T cells stimulated by lysate-pulsed ones. Conclusion : These results indicate the choice of antigen is a critical determinant in the induction of antitumor immunity against malignant glioma. Antigen preparations from GABs represent a promising alternative to glioma cell lysate in DC-based glioma vaccine strategies.

Biological Activities of Soybean Sauce (Kanjang) Supplemented with Deep Sea Water and Sea Tangle (해양심층수 및 다시마 분말을 첨가하여 제조한 간장의 생리활성 효과)

  • Ham, Seung-Shi;Kim, Soo-Hyun;Yoo, Su-Jong;Oh, Hyun-Taek;Choi, Hyun-Jin;Chung, Mi-Ja
    • Food Science and Preservation
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    • v.15 no.2
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    • pp.274-279
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    • 2008
  • This study investigated the antimutagenic and anticancer effects of soybean sauce (kanjang) supplemented with deep sea water and Sea Tangle. The Ames test indicated that kanjang had no mutagenicity but it significantly inhibited mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and 4-nitroquinoline-1-oxide (4NQO). Kanjang (200 ug/plate) with supplementary deep sea water and Sea Tangle had approximately 90.9% and 62.0% inhibitory effect, respectively, against mutagenesis of TA100 induced by MNNG and 4NQO. There was 61.7% inhibition of mutagenesis induced by 4NQO against the TA98 strain. Kanjang inhibited growth of cell lines of human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human gastric carcinoma (AGS), human lung carcinoma (A549), and human breast adenocarcinoma (MCF-7) in a concentration-dependent manner. Treatment with kanjang supplemented with 1.0 mg/mL deep sea water had cytotoxicities of 69.4% 70.5% 55.6% 82.1 % and 73.2% against HeLa, Hep3B, AGS, A549 and MCF-7 cells respectively. In contrast kanjang supplemented with 1 mg/mL deep sea water had only $10{\sim}40%$ cytotoxicity on normal human embryonal kidney cells (293). Kanjang supplemented with deep sea water significantly inhibited tumor growth in mice injected sarcoma-180 cells. In particular, kanjang supplemented with deep sea water (25 mg/kg) inhibited tumor cell activity by 40.9%.

Effects of Gamijinhae-tang (Jiaweizhenke-tang) on Tracheal Smooth Muscle Contraction and Mucin Secretion from Airway Epithelial Cells (가미진해탕(加味鎭咳湯)이 호흡기 점액의 mucin분비에 미치는 영향)

  • Kim, Young-Ho;Joo, Ye-Jin;Jung, Hye-Mi;Seo, Un-Kyo
    • The Journal of Korean Medicine
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    • v.29 no.3
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    • pp.63-75
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    • 2008
  • Objectives: In the present study, the author intended to investigate whether Gamijinhae-tang (Jiaweizhenke-tang) (GJHT) significantly affects both contractility of tracheal smooth muscle and mucin secretion from airway epithelial cells. Materials and Methods: Effect of GJHT on contractility of isolated tracheal smooth muscle of rabbit was investigated. Confluent hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with 3H-glucosamine for 24 hrs and chased for 30 min in the presence of GJHT to assess the effect of the agent on 3H-mucin secretion. At the same time, confluent NCI-H292 cells were chased for 30 min in the presence of GJHT to assess the effect of the agent on MUC5AC secretion by ELISA. Total elution profiles of control spent media and treatment sample (radioactive mucin) through Sepharose CL-4B column were analyzed. Also, effect of the agent on MUC5AC gene expression in cultured NCI-H292 cells was investigated. Possible cytotoxicities of the agent were assessed by measuring both lactate dehydrogenase (LDH) release from HTSE cells and examining the rate of survival and proliferation of NCI-H292 cells. Results: (1) GJHT inhibited Ach-induced contraction of isolated tracheal smooth muscle; (2) GJHT significantly increased mucin secretion from cultured HTSE cells. However, it did not affect MUC5AC secretion from NCI-H292 cells, only chiefly affecting the 'mucin' secretion; (3) GJHT did not significantly affect the expression levels of MUC5AC gene in cultured NCI-H292 cells; (4) GJHT did not significantly inhibit the survival and proliferation of NCI-H292 cells. However, it slightly increased LDH release from HTSE cells. Conclusion: The author suggests that effects of GJHT with their components should be further investigated and it is valuable to find, from oriental medical prescriptions, novel agents which might regulate mucin secretion from airway epithelial cells.

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Biological Activities of the Vaporized Liquid of Water-boiled Pine Needle (솔잎 열수 증류액의 생리활성 효과)

  • Lee Hyo-Jin;Cui Cheng-Bi;Choi Hyung-Taek;Kim Soo-Hyun;Ham Young-An;Lee Deuk-Sik;Ham Seung-Shi
    • Food Science and Preservation
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    • v.12 no.2
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    • pp.179-183
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    • 2005
  • This study was performed to determine the antioxidative, antimutagenic, and anticancer effects of vaporized liquid of water-boiled pine needle(VLP) using DPPH free radical donating method, Ames test, and cytotoxicity. VLP showed the highest electron donating activities $(18.4\;{\mu}L)$. The inhibition rate of VLP $(200\;{\mu}L/plate)$ in the Salmonella. typhimurium TA100 strain showed $45.9\%$ inhibition against the mutagenesis induced by MNNG. In addition, the suppression of with same concentration of VLP in the S. typhimurium TA100 strains showed $85.5\%$ inhibition against 4NQO, respectively. The suppressions under the same condition against Trp-P-1 in the TA98 and TA100 strains were $91.0\%$ and $62.1\%$, respectively. The cytotoxic effects of VLP against the cell lines with human lung carcinoma (A549), human hepatocellular carcinoma (HepG2) , human gastric carcinoma (AGS), human breast adenocarcinoma (MCF-7) and human cervical adenocarcinoma (HeLa) were inhibited with increase of the VLP concentration. The treatment of $50\;{\mu}L/well$ VLP showed strong cytotoxicities of $78.7\%,\;90.3\%,\;90.8\%,\;62.3\%$ and $93.7\%$ against A549, HepG2, AGS, MCF-7 and HeLa, respectively.

Effects of Scutellaria baicalensis Extracts on Tyrosinase Gene Expression in B16 Melanoma Cells (B16 Melanoma Cell에서 티로시나아제 유전자 발현에 황금(Scutellaria baicalensis) 추출물이 미치는 효과)

  • Cho, Nam-Chul;Bai, Suk;Chin, Jong-Eon
    • The Korean Journal of Food And Nutrition
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    • v.23 no.1
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    • pp.118-123
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    • 2010
  • To estimate the regulatory effects of Scutellaria baicalensis extracts on melanin biosynthesis, we evaluated the regulatory effects of the tyrosinase gene on B16 melanoma cells. The results revealed that methanolic extracts of Scutellaria baicalensis resulted in a high increase in the expression of the tyrosinase gene. Specifically, treatment with extracts at concentrations of $10\;{\mu}g/m{\ell}$ and $100\;{\mu}g/m{\ell}$ resulted in increases in tyrosinase gene expression rates of approximately 231% and 256%, respectively, when compared to the control. Moreover, the solvent fraction layers(methylene chloride, ethyl acetate, butyl alcohol, water) improved the expression of the tyrosinase gene, but to a lesser degree than the methanolic extracts. An MTT assay revealed, that the methanolic extract exhibited very low cytotoxicities at $10\;{\mu}g/m{\ell}$ and $100\;{\mu}g/m{\ell}$. Taken together, the results of this study indicated that the methanolic extracts of Scutellaria baicalensis was a very effective positive regulator of tyrosinase gene expression.