• Title, Summary, Keyword: Breast cancer

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Neuroprotective effects of geneticin (G418) via apoptosis in perinatal hypoxic-ischemic brain injury (주산기 저산소성 허혈성 뇌손상에서 항고사를 통한 geneticin (G418)의 신경보호 효과)

  • Ju, Mi;Lee, Hyun Ju;Lee, Sun Ju;Seo, Eo Su;Park, Hye Jin;Lee, Kye Yang;Lee, Gyeong Hoon;Choi, Eun Jin;Kim, Jin Kyung;Lee, Jong Won;Chung, Hai Lee;Kim, Woo Taek
    • Clinical and Experimental Pediatrics
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    • v.51 no.2
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    • pp.170-180
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    • 2008
  • Purpose : Some antibiotics were known to exert neuroprotective effects in the animal model of hypoxic-ischemic (H-I) brain injury, but the mechanism is still unclear. A recent study reported that geneticin (G418), an aminoglycoside antibiotic, increased survival of human breast cancer cells by suppressing apoptosis. We investigated the neuroprotective effects of systemically administrated geneticin via anti-apoptosis following the H-I brain injury Methods : Seven-day-old Sprague-Dawley rat pups were subjected to unilateral (left) common carotid artery occlusion followed by 2.5 hours of hypoxic exposure and the cortical cell culture of rat brain was done under a hypoxic incubator. Apoptosis was measured in the injured hemispheres 7 days after H-I insult and in the injured cells from hypoxic chamber using morphologic analysis by Terminal dUTP Nick-end Labeling(TUNEL) assay and immunohistochemistry for caspase-3, and cytologic analysis by western blot and real time PCR for bax, bcl-2, and caspase-3. Results : The gross appearance and hematoxylin and eosin stain revealed increased brain volume in the geneticin-treated animal model of perinatal H-I brain injury. The TUNEL assay revealed decreased apoptotic cells after administration of geneticin in the cell culture model of anoxia. Immunohistochemistry showed decreased caspase-3 expression in geneticin-treated cortical cell culture. Western blot and real-time PCR showed decreased caspase-3 expression and decreased ratio of Bax/Bcl-2 expression in geneticin-treated animal model. Conclusion : Geneticin appears to exert a neuroprotective effect against perinatal H-I brain injury at least via anti-apoptosis. However, more experiments are needed in order to demonstrate the usefulness of geneticin as a preventive and rescue treatment for H-I brain injuries of neonatal brain.

Physiological Activities of Ginkgo biloba Sarcotesta Extract with Heat Treatment (열처리에 따른 은행 외종피 추출물의 생리활성)

  • Kim, Sung Tae;Lee, Ji Hyun;Lee, Sang Hoon;Jang, Gwi Yeong;Li, Meishan;Kim, Min Young;Yoon, Nara;Lee, Junsoo;Jeong, Heon Sang
    • The Korean Journal of Food And Nutrition
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    • v.28 no.3
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    • pp.369-375
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    • 2015
  • This study was performed to investigate the physiological activities of Ginkgo biloba sarcotesta extracts before and after heat treatment. G. biloba sarcotesta was heated at $130^{\circ}C$ for 2 h and extracted with water, 70% ethanol and 80% methanol. ABTS and DPPH radical scavenging activities increased after heating in the water (14.95 mg AAE/g and 7.36 mg TE/g) and ethanol extracts (12.20 mg AAE/g and 6.23 mg TE/g). ${\alpha}$-Glucosidase inhibitory activity decreased after heating in all but the water extract. Angiotensin converting enzyme I inhibitory activities decreased after heating in all extracts. Nitric oxide production inhibitory activity increased from 12.40~44.55% of the raw sample to 40.76~72.39% of the heated sample at a concentration of $200{\mu}g/mL$. Lipid accumulation inhibitory activities were similar before and after heat treatment. The highest antiproliferative effects on MCF-7 human breast cancer cell lines were observed in 80% methanol extract in the heated sample. Cell viability at concentrations of 25, 50, 100, and $200{\mu}g/mL$ measured 34.88, 17.58, 8.44 and 10.48%, respectively. From the results, the antioxidant and antiproliferative activities of G. biloba sarcotesta extracts increased with heat treatment, and research on the identification of the structure for the active compounds are needed in further studies.

H2AX Directly Interacts with BRCA1 and BARD1 via its NLS and BRCT Domain Respectively in vitro (H2AX의 BRCA1 NLS domain과 BARD1 BRCT domain 각각과의 in vitro 상호 결합)

  • Bae, Seung-Hee;Lee, Sun-Mi;Kim, Su-Mi;Choe, Tae-Boo;Kim, Cha-Soon;Seong, Ki-Moon;Jin, Young-Woo;An, Sung-Kwan
    • KSBB Journal
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    • v.24 no.4
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    • pp.403-409
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    • 2009
  • H2AX, a crucial component of chromatin, is implicated in DNA repair, cell cycle check point and tumor suppression. The aim of this study was to identify direct binding partners of H2AX to regulate cellular responses to above mechanisms. Literature reviews and bioinformatical tools were attempted intensively to find binding partners of H2AX, which resulted in identifying two potential proteins, breast cancer-1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1). Although it has been reported in vivo that BRCA1 co-localizes with H2AX at the site of DNA damage, their biochemical mechanism for H2AX were however only known that the complex monoubiquitinates histone monomers, including unphosphorylated H2AX in vitro. Therefore, it is important to know whether the complex directly interacts with H2AX, and also which regions of these are specifically mediated for the interaction. Using in vitro GST pull-down assay, we present here that BRCA1 and BARD1 directly bind to H2AX. Moreover, through combinational approaches of domain analysis, fragment clonings and in vitro binding assay, we revealed molecular details of the BRCA1-H2AX and BARD1-H2AX complex. These data provide the potential evidence that each of the BRCA1 nuclear localization signal (NLS) and BARD1 BRCA1 C-terminal (BRCT) repeat domain is the novel mediator of H2AX recognition.

Inhibitory Mechanisms of Cell Cycle Regulation Induced by Indole-3-carbinol in Hepatocellular Carci-noma HepG2 Cells. (간암 세포주에서의 Indole-3-Carbinol에 의해 유도되는 세포주기 억제 기전)

  • 김동우;이광수;김민경;조율희;이철훈
    • Microbiology and Biotechnology Letters
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    • v.29 no.3
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    • pp.181-185
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    • 2001
  • The naturally occurring chemical indole-3-carbinol (13C), found in vegetables of the Brassica genus, is a promising anticancer agent that was shown previ- ously to induce a Gl cell cycle arrest of human breast cancer cell lines, independent of estrogen receptor signaling. The anticancer activity of 13C and the possible mechanisms of its action were explored in a human hepatocellular carcinoma cell line, HepG2. Treatment of HepG2 cells with 13C suppressed the growth of the cells. The growth sup- pression caused by 13C ($IC_{50}$/: 444$\mu$M) was found to be partially due to its ability to stop the cell cycle in HepG2 cells. Western blot analysis for the Gl phase artiest demonstrated that the expression-levels of cyclin-dependent kinase (Cdk4, Cdk6) and cyclic D were reduced strongly after treatment of Hep72 cells with 13C (4007M) for 24- 72 hrs. Furthermore, I3C selectively abolished the expression of Cdk6 in a dose- and time-dependent manner, and accordingly, inhibited the phosphorylation of retinoblastoma. Interestingly, after the HepG2 cells reached their max- imal growth arrest, the level of the p21, a well-known Cdk inhibitor, increased significantly. Therefore, it could be considered that the Gl arrest of HepG2 cells treated with 13C was due to the indirect inhibition of Cdk4/6 activities by p21 Western blot analysis for G2/M phase arrest of demonstrated the levels of Cdc2 and cyclin Bl werer reduced dramatically after the treatment of HepG2 cells with 13C ($40\mu$M) for 24-72 hrs. flow cytometry of propidium iodide-stained HepG2 cells revealed that 13C induces a Gl (53%,72hr incubation) and G2 (25%,24hr incubation) cell cycle arrest. Thus, our observations have uncovered a previously undefined antiproliferative pathway for r3C that implicates Cdk4/6 and Cdc2 as a target for cell cycle control in human HepG2 cells. However, the 13C-medi- ated cell cycle arrest and repression of Cdk4/6 production did not affect the apoptotic induction of HepG2 cell.

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Antimutagenic and Cytotoxic Effects of Acer ginnala Max. Bark Extracts (신나무 껍질 추출물의 항돌연변이원성 및 세포독성 효과)

  • Oh Heung-Seok;Cui Cheng-Bi;Choi Hyung-Taek;Kim Soo-Hyun;Jeon Mi-Sun;Ham Seung-Shi
    • Korean Journal of Food Preservation
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    • v.11 no.4
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    • pp.550-556
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    • 2004
  • In the present study, we investigated the antimutagenic and cytotoxic effects of Acer ginnala Max. bark extract on S. typhimurium TA98, TA100 and cancer cell lines with Ames test and SRB assay, respectively. They were extracted with methanol and then fractionated using hexane, chloroform, ethyl acetate, butanol, and water to obtain the fractions. The inhibition rate of methanol ($200\;{\mu}g/plate$) of Acer ginnala Max. bark extract in the Salmonella typhimurium TA100 strain showed $83.3\%$ against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In addition, the suppression of methanol extract with same concentration of in the Salmonella typhimurium TA98 and TA100 strains showed $80.3\%\;and\;92.7\%$ inhibition against 3-amino-1,4-dimethyl-5H-pyrido-(4,3-b)indol (Trp-P-1), respectively. The cytotoxicity effects of Acer ginnala Max. bark extract against the cell lines with human lung carcinoma (A549), human gastric carcinoma (AGS), human hepatocellular carcinoma (Hep3B) and human breast adenocarcinoma (MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL Acer ginnala Max. bark methanol extract of methanol showed strong cytotoxicities of $77.3\%,\;90.4\%,\;88.9\%,\;and\;83.7\%$ against A549, AGS, Hep3B and MCF-7, respectively.

Cytotoxicity and Chemosensitizing Effect of Camellia(Camellia japonica) Tea Extracts (동백엽차와 화차의 세포독성 및 다제내성 극복효과)

  • 황은주;차영주;박민희;이장원;이숙영
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.3
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    • pp.487-493
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    • 2004
  • This study has been undertaken to increase availability of native camellia in Jeonnam as a medicinal resource and to isolate the effective components from them. Fresh leaf and flower of camellia, single camellia tea and camellia tea mixed with green tea, herbs were screened for cytotoxicity on MCF -7 (human breast adenocarcinoma pleual effusion), Calu-6 (human pulmonary carcinoma), SNU-601 (human gastric carcinoma) cells. Also their multidrug-resistance reversing activity were evaluated using drug sensitive AML-2/WT and multidrug-resistant AML-2/D100 cells. Among the camellia extracts, young leaf and camellia tea mixed with green tea had strong growth inhibitory effects in below 100 $\mu\textrm{g}$/mL against human cancer cells. In result, young leaf showed the strongest inhibitory effects on MCF -7 ($IC_{50}$/ = 100 $\mu\textrm{g}$/mL ↑), Calu-6 ($IC_{50}$/ = 79 $\mu\textrm{g}$/mL), and SNU -601 ($IC_{50}$/ = 39 $\mu\textrm{g}$/mL), and AML-2/WT ($IC_{50}$/ = 64 $\mu\textrm{g}$/mL). Chemosensitizing effect was the extracts of mature leaf ($IC_{50}$/ = 97 $\mu\textrm{g}$/mL, RF=3.0), roasted tea ($IC_{50}$/ = 76 $\mu\textrm{g}$/mL, RF = 2.6 ↑) and steam tea ($IC_{50}$/ = 70 $\mu\textrm{g}$/mL, RF=2.8 ↑) strongly potentiate vincristine cytotoxicity in AML-2/D100 cells. But their cytotoxicities to both sensitive AML-2/WT and resistant AML-2/D100 cells were in the same order of magnitude. This results indicate that crude extracts of camellia mature leaves would contain some principles which have chemosensitizing activity.

Biological Activity of Ixeris dentata Nakai juice Extracts (씀바귀(Ixeris dentata Nakai) 생즙 추출물의 생리활성)

  • 김명조;김주성;강원희;조미애;함승시;정동명
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.5
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    • pp.924-930
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    • 2002
  • Ixeris dentata extracts exllibited antimicrobial activity against some bacteria and fungi. Also EtOH extracts showed strong antioxidant activity and RC$_{50}$ value was 28 $\mu\textrm{g}$/mL. The inhibitory effect of Ixeris dentata on the mutagenicity in Salmonella and cytotoxicity on cancer cell were studied. Ixeris dentata extracts showed anti-mutagenic effects of 78.83 and 75.96% on B(a)P in S. typhimurium TA98 and Th100, respectively. These extracts showed 78.72% antimutagenicity on TA100 against MNNG. The Ixeris dentata extract with strong antimutagenic activities was further fractionated by hexane, ethyl acetate, butanol and water. Butanol fraction was found to be highest in antimutagenic activity against MNNG than the other fractions. Butanol fraction of Ixreis dentate revealed the highest cytotoxicity against AS49 human lung carcinoma cells in which cell growth was inhibited by 93.75% at 375 $\mu\textrm{g}$/mL. Hexane fraction of ixeris dentate exhibited 68.56% inhibition against MCF-7 human breast adenocarcinoma cells at 500 $\mu\textrm{g}$/mL. Hexane fraction of Ixeris dentata exhibited 84.91% inhibition against Hep 3B human hepatocellular carcinoma cells at 500 $\mu\textrm{g}$/mL. From these results, it is considered that Ixeris dentata has strong antimutagenic and anticancer effects in vitro. However, these extracts and fractions did not show any cytotoxic effect against 293 cells.

Antioxidative, Antimutagenic and Cytotoxic Effects of Natural Seasoning Using Lentinus edodes Powder (표고버섯 분말을 첨가한 천연 조미료 추출물의 항산화성, 항돌연변이성 및 세포독성 효과)

  • Yoo, Su-Jung;Kim, Soo-Hyun;Choi, Houng-Taek;Oh, Hyun-Taek;Choi, Hyun-Jin;Ham, Seung-Shi
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.5
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    • pp.515-520
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    • 2007
  • This study was peformed to determine the antioxidative, antimutagenic and cytotoxic effects of the natural seasoning using Lentinus edodes powder (NSLP) by DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical donating method, Ames test, and cytotoxicity, respectively. The scavenging effect on DPPH radical in ethyl acetate fraction of NSLP showed $155{\mu}g\;of\;RC_{50}$. The direct antimutagenic effects of ethanol extract and its solvent fractions of NSLP were examined by Ames test using Salmonella Typhimurium TA98 and TA100. In the Ames test, ethanol extract of NSLP alone did not exhibit any mutagenicity and most of the samples showed high antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitroso guanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). Ethyl acetate fraction of NSLP ($200{\mu}g/plate$) showed approximately 82% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 84% and 80% inhibitions were observed on the mutagenesis induced by 4NQO and MNNG against TA100 strain. In anticancer effects of ethanol extract and its solvent fractions of NSLP against cancer cell lines including human lung carcinoma (A549), human breast adenocarcinoma (MCF-7), human hepatocellular carcinoma (Hep3B), human cervical adenocarcinoma (HeLa) and human gastric carcinoma (AGS) were investigated. The treatment of 1 mg/mL ethyl acetate fraction of NSLP showed strong cytotoxicity of 56.7%, 84.9%, 64.6%, 85.1% and 71.5% against A549, MCF-7, Hep3B, HeLa and AGS, respectively. In contrast 1 mg/mL treatment of NSLP extract and its solvent fractions had only $4{\sim}40%$ cytotoxicity on human transfomed primary embryonal kidney cell (293). From this result, it is suggested that NSLP is believed to have possible antioxidative, antimutagenic and anticancer capacities.

Antimutagenic and Antitumor Effects of Codonopsis lanceolata Extracts (더덕 추출물의 항돌연변이 및 항종양 효과)

  • Kim, Soo-Hyun;Choi, Hyun-Jin;Chung, Mi-Ja;Cui, Cheng-Bi;Ham, Seung-Shi
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.10
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    • pp.1295-1301
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    • 2009
  • This study was carried out to investigate the mutagenic, antimutagenic, cytotoxicity and antitumor effect of Codonopsis lanceolata (CL). CL was extracted with 70% ethanol and then further fractionated to hexane, chloroform, ethyl acetate, butanol and water. Antimutagenic, cytotoxicity and antitumor effects of CL extracts were measured by using Ames test, SRB method, and the tumor growth inhibition test. CL extracts did not show any mutagenicity in the Ames test; however, 70% ethanol extracts and its fractions had strong antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). The ethyl acetate fraction of CL (200 ${\mu}g$/plate) showed approximately 72.1% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 69.6% and 67.0% inhibitions were observed on the mutagenesis induced by MNNG and 4NQO against TA100 strain. In anticancer effects, the cytotoxicity of CL extract and its fractions against cancer cell lines including human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (HepG2), human breast adenocarcinoma (MCF-7), human lung carcinoma (A549) and transformed primary human embryo kidney (293) were investigated. The treatment of 1 mg/mL CL ethyl acetate fraction had the highest cytotoxicity of 74.5%, 70.7% and 80.3% against HeLa, MCF-7 and A549 cells, respectively. In contrast, the extract and its fractions showed only 2$\sim$31% cytotoxicity for a normal human kidney cell line (293). In vivo anticancer effect of CL extract was tested using Balb/c mice transplanted sarcoma-180 cells. CL ethyl acetate fraction showed the highest inhibition rate of 56.4% at the 50 mg/kg concentration.

Enhancement of Anticancer Activity of Acer mono by High Pressure Extraction Process (고로쇠 수피 초고압 추출물의 항암활성 증진)

  • Jeong, Myoung-Hoon;Kim, Seung-Seop;Ha, Ji-Hye;Jin, Ling;Lee, Hak-Ju;Kang, Ha-Young;Park, Sung-Jin;Lee, Hyeon-Yong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.9
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    • pp.1243-1252
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    • 2009
  • We investigated a method to improve anticancer activities of Acer mono by ultra high pressure extraction process. The extract yields by ultra high pressure were 9.49% and 9.87% for 5 min and 15 min processing time, respectively, which were relatively higher than 3$\sim$4% of conventional extraction processes due to their resid bark structure. The extract for 15 minutes extraction (HPE15) showed higher potent scavenging effect as 94.56% than the control, BHA as 93.24%. On SOD-like test, HPE15 also showed the highest activity as 38.6% at 1.0 mg/mL concentration. The cytotoxicity of HPE15 on normal human lung and kidney cell were below 23.54% in adding 1.0 mg/mL. Generally, human cancer cell growth stomach adenocarcinoma (AGS), lung adenocarcinoma (A549), breast adenocarcinoma (MCF-7), colon adenocarcinoma (Caco-2) and liver adenocarcinoma (Hep3B) were inhibited up to 75% with higher selectivity of above 4.0. High antioxidant activity of HPE15 resulted in high anticancer activity, and its activity was also due to higher yields of Acer mono by ultra high pressure extraction process. It was also proved by HPLC comparison analysis.