• Title/Summary/Keyword: cytotoxic activities

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Antioxidant and anticancer properties of hot water and ethanol extracts from the roots of Smilax china L. (발계(Smilax china L.) 열수 및 에탄올 추출물의 항산화 및 항암활성)

  • Kim, Ye Jin;Son, Dae-Yeul
    • Food Science and Preservation
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    • v.20 no.5
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    • pp.691-698
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    • 2013
  • The biological activities of Smilax china L. rhizome (SCR), hot water (SCRW) and 70% ethanol extract (SCRE) were analyzed. The total phenolic contents of SCRW and SCRE were 51.7 and 100.5 mg/g, respectively. The measured flavonoid content of SCRW ($67.7{\mu}g/g$) was almost double that of SCRE ($31.7{\mu}g/g$). SCRE ($IC_{50}=42.4{\mu}g/mL$) exhibited stronger antioxidant activity in the DPPH system than the positive control ${\alpha}$-tocopherol ($71.3{\mu}g/mL$) or butylated hydroxy anisole ($53.8{\mu}g/mL$) did. SCRE ($IC_{50}=50.3{\mu}g/mL$) also showed stronger ABTS radical scavenging activity, as did ${\alpha}$-tocopherol ($67.1{\mu}g/mL$). The SOD-like activity and Tyrosinase inhibition activity of SCRW and SCRE showed almost the same pattern. The best SOD-like activity and tyrosinase inhibition activity were measured as 24.9% and 20.3% in SCRW at $1,000{\mu}g/mL$, respectively. The cytotoxic effects of the SCR extracts were analyzed via MTT assay on human cancer and normal cells. SCRW and SCRE did not show cytotoxicity up to the concentration of $1,000{\mu}g/mL$ against the normal human cell line HEK293. Against human breast cancer cells (MCF-7), SCRW inhibited MCF-7 growth (by 27.6%) better than the anticancer drug cyclophosphamide (15.5%) at $1,000{\mu}g/mL$. SCRE ($1,000{\mu}g/mL$) inhibited the growth of human lung cancer cells A549 (37.6%) and human stomach cancer cells AGS (53.6%) more effective than did SCRW (21.0% and 35.4%) or CPA (22.2% and 31.7%). These results suggest the potential use of SCRE and SCRW as an excellent antioxidant and antiproliferative substance, respectively.

Effects of Regional Hyperthermia with Moderate Temperature on Cancer Treatment (국부 중등도 온열요법의 암치료 효과)

  • Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.26 no.9
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    • pp.1088-1096
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    • 2016
  • Despite that moderate hyperthermia can exert various antitumor activities such as direct cytotoxic effects on tumor cells, effects on tumor vasculatures and immunological effects, hyperthermia has been usually combined with radiotherapy or chemotherapy due to its limited efficacy in cancer treatment, showing some positive clinical benefits with generally well-tolerated side effects. Since heat shock responses itself can interfere with the anti-tumor effects of hyperthermia, not all of these studies might have demonstrated positive clinical outcomes in cancer patients. Therefore, the negative anti-tumor effect of hyperthermia should be reduced to enhance the effectiveness of hyperthermia. Although the responses to heat stress of tumor tissues containing vessels, immune cells, connective tissues as well as cancer cells, are very complicated, it is needed to study in the near future if some clinically available drugs, which can modulate heat stress responses, can improve the efficacy of hyperthermia in patients with cancer. In this review, the effect of clinical hyperthermia centered on non-invasive external hyperthermia using radiofrequency at moderate temperature will be discussed, since it is the state-of-the-art technology in the current clinical practice of hyperthermia, and a moderate operational temperature is used to increase the therapeutic effectiveness of conventional therapy without additional toxicity to normal tissues.

Anti-Inflammatory Effect of Sedum takesimense Nakai Water Extract in RAW 264.7 Cells (섬기린초 물 추출물의 마우스 대식세포에서 항염증 효능)

  • Jang, Ji Hun;Jung, Ho Kyung;Ko, Jae Hyung;Sim, Mi Ok;Woo, Kyeong Wan;Kim, Tae Muk;Lee, Ki Ho;Ahn, Byeong Kwan;Cho, Hyun Woo;Cho, Jung Hee;Jung, Won Seok
    • Korean Journal of Medicinal Crop Science
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    • v.24 no.3
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    • pp.228-236
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    • 2016
  • Background: Sedum takesimense Nakai has been used as folk medicine in Korea. The present study aimed to determine the biological activity of S. takesimense by investigating the anti-inflammatory effects of S. takesimense water extract (SKLC) on the lipopolysaccharide-induced inflammatory response in RAW 264.7 cells. Methods and Results: Cytotoxicity of SKLC on RAW 264.7 cells was determinded by performing MTS assay was found to have no cytotoxic effect on RAW 264.7 cells at a concentration range of $62-500{\mu}g/m{\ell}$. Further, pretreatment of SKLC inhibited lipopolysaccharide-induced nitric oxide (NO) production in a dose-dependent manner. To determined the inhibitory mechanisms of SKLC on inflammatory mediators, we assessed the inducible nitric oxide synthase (iNOS) and cyclooxygnease-2 (COX-2) pathways. The activities of these pathways were decreased in a dose-dependent manner by SKLC. The production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin $(IL)-1{\beta}$, and IL-6 were also reduced. Conclusions: These results suggest that the down regulation of iNOS, COX-2, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 expression by SKLC are mediated by the down regulation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity, a transcription factor necessary for pro-inflammatory mediators. This might be the mechanism underlying the anti-inflammatory effects of SKLC.

Effects of Sotosaja-hwan on the Generation of ROS, RNS, and on the Expression of NF-${\kappa}B$-dependent Proteins in ob/ob Mouse (소도사자환이 ob/ob mouse에서 ROS/ RNS 생성 억제 및 NF-${\kappa}B$ 의존성 단백질에 미치는 영향)

  • Bang, Yong-Suk;Jeong, Ji-Cheon
    • The Journal of Korean Medicine
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    • v.30 no.1
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    • pp.51-63
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    • 2009
  • Objectives: Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}{O_2}^-$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of $ONOO^-$, NO and ${\cdot}{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}{O_2}^-$ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.

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Utilization of [6]-gingerol as an origin discriminant marker influencing melanin inhibitory activity relative to its content in Pinellia ternata (반하(Pinellia ternata)에서의 [6]-gingerol 함량과 멜라닌 저해 활성에 영향을 미치는 원산지 판별 마커로의 활용)

  • An, Ju Hyeon;Won, Hyo Jun;Seo, Soo-Kyung;Kim, Doo-Young;Ku, Chang-Sub;Oh, Sei-Ryang;Ryu, Hyung Won
    • Journal of Applied Biological Chemistry
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    • v.59 no.4
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    • pp.323-330
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    • 2016
  • Pinellia ternata Breitenbach, the natural medicinal plant of the Araceae family, is a perennial plant originated from the East Asia, but also widely distributed in Europe and North America. Its tuber is used as traditional medicine for treatment of various diseases such as vomiting, inflammation, and traumatic injury. Pharmacological studies revealed that P. ternata possesses anticonvulsant, anti-tumor, insecticidal, and cytotoxic activities. Despite being well-known as the useful medicinal plant, there is no reliable, standardized method for origin discrimination. Ultra performance liquid chromatography-photodiode array detector and quadrupole time of flight-mass spectrometry based metabolite-profiling was applied to explore significant metabolite for origin discrimination between Korean and Chinese P. ternata. One compound was isolated from Korean P. ternata using repeated ODS column chromatography by bioactivity guided fractionation, and determined as [6]-gingerol according to the results of spectroscopic data including nuclear magnetic resonance and MS. This compound was selected as cosmeceutical biomarker by fingerprints, and it was associated to melanin inhibitory effect determining its origin authenticity. Furthermore, the calibration curve of biomarker was prepared using validated method for the comparison of content between Korean and Chinese P. ternata. This is the report to address the selection and successful validation of the discriminant metabolite for confirmation of Korean P. ternata.

Inhibition of DNA-dependent Protein Kinase by Blocking Interaction between Ku Complex and Catalytic Subunit of DNA-dependent Protein Kinase

  • Kim, Chung-Hui;Cuong, Dang-Van;Kim, Jong-Su;Kim, Na-Ri;Kim, Eui-Yong;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.1
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    • pp.9-14
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    • 2003
  • Recent studies indicated that cancer cells become resistant to ionizing radiation (IR) and chemotherapy drugs by enhanced DNA repair of the lesions. Therefore, it is expected to increase the killing of cancer cells and reduce drug resistance by inhibiting DNA repair pathways that tumor cells rely on to escape chemotherapy. There are a number of key human DNA repair pathways which depend on multimeric polypeptide activities. For example, Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) on binding to double strand DNA breaks (DSBs) are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and are essential for DNA-dependent protein kinase (DNA-PK) activity. It has been known that DNA-PK is an important factor for DNA repair and also is a sensor-transmitting damage signal to downstream targets, leading to cell cycles arrest. Our ultimate goal is to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. This would greatly facilitate tumor cell cytotoxic activity and programmed cell death through DNA damaging drug treatment. Therefore, we designed a domain of Ku80 mutants that binds to Ku70 but not DNA end binding activity and used the peptide in co-therapy strategy to see whether the targeted inhibition of DNA-PK activity sensitized breast cancer cells to irradiation or chemotherapy drug. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, thus resulting in inactivation of DNA-PK activity. Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to IR or chemotherapy drugs, and the growth of breast cancer cells was inhibited. Additionally, the results obtained in the present study also support the physiological role of resistance of cancer cells to IR or chemotherapy.

Invitro and Virtual Screening of Bioactive Molecule from Mycelium of Trichoderma atroviride Inhibit the UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine Deacetylases (LpxC) for Treatment of Bacterial Infection

  • Saravanakumar, Kandasamy;Park, Cheol-Ho;Wang, Myeong-Hyeon
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.04a
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    • pp.67-67
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    • 2018
  • Trichoderma species are a rich source of metabolites, but less known for biomedical potential. This work deals with antibacterial and antioxidant potentials of intracellular non-cytotoxic metabolites, extracted from Trichoderma atroviride (KNUP001). A total of 53 fractions was collected by column chromatography and tested for cytotoxicity by MTT assay. Only one fraction (F41) was found to be non-toxic to Vero cells with $95.4{\pm}0.61%$ of survival. The F41 was then subjected to chemical analysis, antibacterial and antioxidant assays. The F41 at $500{\mu}g.ml^{-1}$ showed the total antioxidant of $48.70{\pm}2.90%$, DPPH radical scavenging activity of $37.25{\pm}2.25$, nitric oxide (NO) radical scavenging activity of $54.55{\pm}1.95$ and $H_2O_2$ radical scavenging activity of $43.75{\pm}3.21$. The F41 at $25{\mu}g.ml^{-1}$ displayed antibacterial activity against E. coli ($14.25{\pm}0.2mm$), P. mirabilis ($10.4{\pm}0.6mm$), S. dysenteriae ($18.6{\pm}03mm$), S. paratyphi A ($14.1{\pm}1.1mm$), E. aerogenes ($5.6{\pm}0.4mm$) and S. marcescens ($14.25{\pm}0.2mm$). GC-MS analysis revealed the dominant presence of oleic acid C 18.1 (63.18%), n-hexadecanoic acid (6.17%), and ethyl oleate (4.93%) and potent molecules such as 8-[(2E)-2-(3-hydroxybenzylidene)hydrazinyl]-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione, 2-(Dimethylamino)ethyl (1Z)-N-hydroxy-2-(4-morpholinyl)-2-oxoethanimidothioate, Fluorene in the F41, and virtual study revealed that these molecules are likely responsible for the antibacterial activities of F41. Hence, further investigation deserves on purification and characterization of the active metabolites from T. atroviride strain KNUP001 towards developing molecular leads to effective antibacterial drugs, and non-toxic to host cells.

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Growth Inhibitory and Quinone Reductase Induction Activities of Salicornia herbacea L. Fractions on Human Cancer Cell Lines in vitro (함초 분획물의 in vitro에서의 암세포 성장억제 및 Quinone Reductase 활성 유도 효과)

  • Jung, Bok-Mi;Park, Jung-Ae;Bae, Song-Ja
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.2
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    • pp.148-153
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    • 2008
  • We investigated the growth inhibitory effect of Salicornia herbacea L. (SH) on human cancer cell lines in vitro. SH was extracted with methanol (SHM), followed by further fractionation into four subfractions according to polarity: hexane (SHMH), methanol (SHMM), butanol (SHMB), and aqueous (SHMA) soluble fractions. We determined the growth inhibitory effect of these fractions against human cancer cell lines using MTT assay. Among the four subfractions of SHM, the SHMM showed the strongest cytotoxic effects on cancer cell lines. We also observed quinone reductase (QR)-inducing effect of methanol layer (SHMM) on HepG2 cells and it was determined to be 3.00 at $100\;{\mu}g/mL$ level compared to the control value of 1.0. The SHMM showed the highest induction activity of quinone reductase on HepG2 cells among the partition layers. The present work suggests that SH merits further study to confirm its chemopreventive potential.

Antioxidative and Biological Activities of Santalum album Extracts by Extracting Methods (추출방법에 따른 백단향의 항산화 및 생리활성)

  • Kim, Tae-Hoon
    • Food Science and Preservation
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    • v.15 no.3
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    • pp.456-460
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    • 2008
  • Santalum album has been used as a folk medicine for treatment of skin diseases, inflammation, gonorrhea, gleet, and cystitis in India and other Asian countries. In a search for possible bioactive agents from natural sources, we found that the various solvent extracts of S. album showed significant antioxidative effect in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity test and moderate other biological functions submitted to the several bioassay systems for whitening and cytotoxicity evaluations. Among the tested extracts displayed DPPH radical scavenging activity, and the 70% acetone extract showed the most potent activity with an $IC_{50}$ value of $18.6\;{\mu}g/ml$, more potent than a positive control, L-ascorbic acid ($IC_{50}$, $28.7\;{\mu}g/mL$). Also, anti-lipid peroxidation, tyrosinase inhibitory, and cytotoxic effects were determined in each experiment. Total phenolic content of 70% acetone extract was found to be 117.1 mg equivalent of gallic acid per g of extract. Previous phytochemical investigation reveals the presence of phenolic compounds. The results indicate that S. album possess potential antioxidant activity and phenolic constituents are responsible for this capacity.

Effects of Antimicrobial and Cytotoxicity of Undaria pinnatifida Sporophyll Fractions (미역귀 분획물의 항균 · 암세포 성장저지 효과)

  • Park, Soung-Young;Jung, Young-Hwa;Shin, Mi-Ok;Jung, Bok-Mi;Bae, Song-Ja
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.6
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    • pp.765-770
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    • 2005
  • In this study, we investigated antimicrobial and cytotoxicity effects of Undaria pinnatifida Sporophyll, which using methanol, dichloromethane and ethanol were extracted and fractionated into four different types: methanol (UPMM), hexane (UPMH), butanol (UPMB) and aqueous (UPMA). The antimicrobial activity was increased in proportion to its concentration by the paper disc method. Among the solvent fractions, UPMM and UPMB showed relatively strong antimicrobial activities in the order. Among various partition layers, the methanol partition layer (UPMM) was showed the strongest cytotoxic effects on all cancer cell lines. We also observed quinone reductase (QR) induced effects in all fraction layers of UP on HepG2 cells. The QR induced effects of UPMH on HepG2 cells at $320\mu g/mL$ concentration indicated 2.36 with a control value of 1.0.