• Title/Summary/Keyword: cancer cell growth inhibition

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Targeted Therapies and Radiation for the Treatment of Head and Neck Cancer (두경부 암의 표적 지향적 방사선 치료)

  • Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.22 no.2
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    • pp.77-90
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    • 2004
  • Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

Mechanism of Inhibition of HepG2 Cell Proliferation by a Glycoprotein from Hizikia fusiformis (톳(Hizikia fusiformis) 당단백질에 의한 HepG2 세포 증식 억제기전)

  • Ryu, Jina;Hwang, Hye-Jung;Kim, In-Hye;Nam, Taek-Jeong
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.45 no.6
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    • pp.553-560
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    • 2012
  • Hizikia fusiformis, a brown alga that is widely consumed in Korea, Japan, and China, possesses a number of potentially beneficial compounds, including antioxidants and anticoagulants. However, the molecular mechanisms of H. fusiformis in hepatoma cells have not been elucidated. This study investigated the antiproliferative effect and mechanism of action of a glycoprotein from H. fusiformis (HFGP) in HepG2 human hepatoma cells. In an MTS assay, 25 ${\mu}g/mL$ HFGP inhibited the proliferation of HepG2 cells by $52.36{\pm}2.37%$. HFGP caused the dose-dependent growth inhibition of HepG2 cells by inducing apoptosis and a sub-G1 phase arrest. The antiproliferative activity of HFGP was confirmed based on the expression of several apoptosis-related proteins, which was assessed by Western blot analysis. The expressions of Fas, Fas-associated death domain protein, Bax, and Bad was significantly up-regulated in HFGP-treated cells, and HFGP induced the translocation of Bax to mitochondria and the release of cytochrome c into the cytosol. Therefore, HFGP might be useful in the treatment of liver cancer.

Syntheses and Evaluations of Antitumor and Antiangiogenic Phthalate Polymers Containing 5-Fluorouracil and Carboxylates

  • Lee, Sun-Mi;Jung, Sang-Wook;Ha, Chang-Sik;Chung, Il-Doo;Lee, Won-Ki;Park, Yong-Ho
    • Macromolecular Research
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    • v.16 no.6
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    • pp.510-516
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    • 2008
  • New antitumor active polymers, poly(methacryloyl-2-oxy-1,2,3-propanetricarboxylic acid-co-exo-3,6-epoxy-l,2,3,6-tetrahydrophthalic acid) [poly(MTCA-co-ETAc)], poly(methacryloyl-2-oxy-l,2,3-propanetricarboxylic acid-co-hydrogen ethyl-exo-3,6-epoxy-l,2,3,6-tetrahydrophthalate) [poly(MTCA-co-HEET)], and poly(methacryloyl-2-oxy-l,2,3-propanetricarboxylic acid-co-a-ethoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil) [poly(MTCA-co-EETFU)] were synthesized and characterized. Their antitumor activity, inhibition of DNA replication and antiangiogenesis were examined. The structures of the polymers were identified by FT-IR, $^1H$ and $^{13}C$-NMR spectroscopy. The number average molecular weights of the fractionated polymers determined by GPC ranged from 9,400 to 14,900, and polydispersity indices were less than 1.7. The in vitro cytotoxicity of these polymers was determined and their antitumor activity was evaluated. The $IC_{50}$ values (the drug concentration at inhibition of 50% tumor growth) indicated that the synthesized polymers were much better inhibitors of cancer cells and showed lower cytotoxicity than the free 5-FU. The in vivo antitumor activity of the conjugates was examined using mice bearing the sarcoma 180 tumor cell line. The life spans (TIC) of the mice treated with the conjugates were higher than those treated with the free 5-FU. In addition, the synthesized conjugates showed excellent antiangiogenic activity based on an embryo chorioallantoic membrane assay.

Determination of Bioactive Compounds and Anti-cancer Effect from Extracts of Korean Cabbage and Cabbage (배추와 양배추 추출물의 생리활성 물질 및 암세포 증식 억제효과 분석)

  • Hwang, Eun-Sun;Hong, Eun-Young;Kim, Gun-Hee
    • The Korean Journal of Food And Nutrition
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    • v.25 no.2
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    • pp.259-265
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    • 2012
  • In this study, we determined total polyphenol content(TPC) and total flavonoid content(TFC) of extracts from Korean cabbage and cabbage using a spectrophotometric method as well as glucosinolates concentration by HPLC. TPCs of Korean cabbage and cabbage extracts were 308.48 ${\mu}g$ GAE/g dry weight and 344.75 ${\mu}g$ GAE/g dry weight, respectively. TFCs of Korean cabbage and cabbage extracts were 5.33 ${\mu}g$ QE/g dry weight and 5.95 ${\mu}g$ QE/g dry weight, respectively. We found six different glucosinolates, namely progoitrin, glucoalyssin, gluconapin, glucobrassicanapin, glucobrassicin and 4-methoxyglucobrassicin in the Korean cabbage extract. In the cabbage extract, there was four glucosinolates, namely glucoraphanin, sinigrin, glucobrassicin and 4-methoxyglucobrassicin. We determined the cytotoxic effect of Korean cabbage and cabbage extracts in AGS human stomach cancer cells, HepG2 human hepatic cancer cells and LNCaP human prostate cancer cells by MTT assay. Dose-dependent relationships were found between the extract concentrations and cancer cell growth inhibition. The overall results support that both Korean cabbage and cabbage, the major vegetables in Korea, contain bioactive compounds such as polypheol, flavonoids as well as glucosinolates and they may play a positive role in cancer prevention.

3,3'-Diindolylmethane (DIM) decrease adhesion, migration and invasion in human prostate cancer cells (3,3'-Diindolylmethane (DIM)이 인체 전립선암 세포의 부착, 이동 및 침윤성에 미치는 영향)

  • Kim, Hyeon-A
    • Food Science and Preservation
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    • v.22 no.1
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    • pp.19-26
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    • 2015
  • Indole 3-carbinol (I3C), important component of cruciferous vegetables and its major acid-catalyzed metabolite, 3,3'-diindolylmethane (DIM) have been suggested to have an inhibitory effect on the tumor growth and metastasis. This study investigated the effect of DIM on the adhesion, migration and invasion of highly invasive PC3 and DU145 human prostate cancer cell lines. Cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 3.0 g/L glucose, 3.7 g/L sodium bicarbonate and 10% fetal bovine and were incubated in a humidified incubator at $37^{\circ}C$ and 5% $CO_2$. DIM reduced the adhesion of PC3 and DU145 cells in a dose dependent manner. The pretreatment of PC3 cells with DIM reduced the adhesion dose dependantly, but inhibition was less effective than the treatment with DIM during the adhesion assay. The migration and invasion of PC3 and DU145 cells were reduced by DIM dose dependantly, and the inhibition of DIM was less effective in the DU145 cells than in the PC3 cells. The pretreatment of PC3 cells with DIM for 24 hr before the assay reduced invasion of PC3 cells by 37%. These results suggest that DIM inhibits adhesion, migration and invasion of the PC3 and DU145 cells and may be an effective antimetastatic therapy in addition to traditional chemotherapy.

Growth-inhibitory Effect of the Solar Salt-Doenjang on Cancer Cells, AGS and HT-29 (천일염으로 제조한 된장의 암세포 성장 억제효과)

  • Lee, Sun-Mi;Chang, Hae-Choon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.12
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    • pp.1664-1671
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    • 2009
  • Doenjang was prepared by using Bacillus subtilis DJI starter and purified salt or solar salt with 12% (w/w) concentration. The prepared Doenjangs were fermented and ripened for 2 month and 16 month, respectively. MTT assay was used to measure the growth-inhibitory effect of Doenjang extracts (water, methanol) on BJ (human foreskin normal cell), HT-29 (human colon cancer cell) and AGS (human gastric adenocarcinoma cell). The anticancer effect increased in both purified salt-Doenjang and solar salt-Doenjang as fermentation period increased. Moreover in the case of water extracts, solar salt-Doenjang (growth inhibitory rate; AGS: 50%, HT-29: 44%) showed definitely higher anticancer effect than purified salt-Doenjang (AGS: 32%, HT-29: 32%). In addition, apoptosis were observed when the water extracts of the Doenjangs were treated into AGS. In particular, it was observed that more apoptosis occured in solar salt-Doenjang treats than purified salt-Doenjang treats. These results suggested that prolonging the fermentation with addition of solar-salt when making Doenjang increased its anticancer effect via cancer cell growth inhibition induced by apoptosis process.

In vitro studies of anti-inflammatory and anticancer activities of organic solvent extracts from cultured marine microalgae

  • Samarakoon, Kalpa W.;Ko, Ju-Young;Shah, Md. Mahfuzur Rahman;Lee, Ji-Hyeok;Kang, Min-Cheol;Kwon, O-Nam;Lee, Joon-Baek;Jeon, You-Jin
    • ALGAE
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    • v.28 no.1
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    • pp.111-119
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    • 2013
  • Marine microalgae are a promising source of organisms that can be cultured and targeted to isolate the broad spectrum of functional metabolites. In this study, two species of cyanobacteria, Chlorella ovalis Butcher and Nannchloropsis oculata Droop, one species of bacillariophyta, Phaeoductylum tricornutum Bohlin, and one species of Dinophyceae, Amphidinium carterae (Hulburt) were cultured and biomasses used to evaluate the proximate comical compositions. Among the determined proximate chemical compositions of the cultured marine microalgae, the highest content of crude proteins and lipids were exhibited in P. tricornutum and A. carterae, respectively. Solvent-solvent partition chromatography was subjected to fractionate each of the cultured species and separated n-hexane, chloroform, ethyl acetate, and aqueous fractions. Nitric oxide production inhibitory level (%) and cytotoxicity effect on lipo-polysaccharide-induced RAW 264.7 macrophages were performed to determine the anti-inflammatory activity. N. oculata hexane and chloroform fractions showed significantly the strongest anti-inflammatory activity at $6.25{\mu}g\;mL^{-1}$ concentration. The cancer cell growth inhibition (%) was determined on three different cell lines including HL-60 (a human promyelocytic leukemia cell line), A549 (a human lung carcinoma cell line), and B16F10 (a mouse melanoma cell line), respectively. Among the extracts, C. ovalis ethyl acetate and A. carterae chloroform fractions suppressed the growth of HL-60 cells significantly at 25 and $50{\mu}g\;mL^{-1}$ concentrations. Thus, the cultured marine microalgae solvent extracts may have potentiality to isolate pharmacologically active metabolites further using advance chromatographic steps. Hence, the cultured marine microalgae can be described as a good candidate for the future therapeutic uses.

G1 Arrest of the Cell Cycle by Gomisin N, a Dibenzocyclooctadiene Lignan, Isolated from Schizandra chinensis Baill in Human Leukemia U937 Cells (오미자에서 분리된 dibenzocyclooctadiene lignan의 일종인 gomisin N에 의한 인체혈구암세포의 세포주기 G1 arrest 유발)

  • Park, Cheol;Hwang, Hye-Jin;Choi, Byung-Tae;Choi, Tae-Hyun;Kim, Byung-Woo;Choi, Young-Whan;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.20 no.7
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    • pp.977-982
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    • 2010
  • We investigated the anti-cancer effects of two dibenzocyclooctadiene lignans, gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in human promyelocytic U937 cells. Gomisin N, but not gomisin A, inhibited cell growth in a concentration-dependent manner, which was associated with the induction of G1 arrest of the cell cycle. G1 arrest induced by gomisin N was correlated with down-regulation of cyclin E, cyclin-dependent kinase (Cdk) 2 and Cdk4, and a concomitant up-regulation of Cdk inhibitors such as p16 (INK4A) and p21 (WAF1/CIP1). Furthermore, gomisin N inhibited phosphorylation of retinoblastoma protein (pRB) and p130, and expression of transcription factor E2Fs. The results indicated that growth inhibition by gomisin N is related to cell cycle arrest at G1 in U937 cells and these findings suggest that gomisin N may be a useful chemotherapeutic agent.

The Antioxidative and Antitumor Activity of Extracts of Agrimonia pilosa (선학초 추출물의 항산화 및 항암활성)

  • Min, Kyung-Jin;Song, Jin-Wook;Cha, Chun-Geun
    • Journal of Food Hygiene and Safety
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    • v.23 no.2
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    • pp.149-156
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    • 2008
  • This study was carried out to investigate the anti oxidative and antitumor activities of medicinal plants for the purpose of developing a functional food. The methanol extracts of Agrimonia pilosa was fractionated with five solvents and examined anti oxidative activities and enzyme inhibitory activities in addition to growth inhibitory activity of human cancer cell. The contents of total phenol compounds in EtOAc and BuOH fraction were 39.89% and 39.56%, respectively. Strong electron donating abilities(>90%) were shown in these fractions and its abilities were 92.90% ($500\;{\mu}g/ml$), 94.47% ($1000\;{\mu}g/ml$) in EtOAc fraction and 93.77% ($500\;{\mu}g/ml$), 92.90% ($1000\;{\mu}g/ml$) in BuOH fraction, respectively. These fractions exhibited more than 50% nitrite scavenging ability and potent inhibition activities to XOase activity (93.06%, 91.73%) at concentration of $1000\;{\mu}g/ml$. In antitumor activity test, hexane fraction showed the strongest growth inhibition activity against HT-29, SNU-1 and HeLa cells. Inhibition levels were 51.50, 90.09% in HT-29, 88.19, 95.11 % in SNU-1 and 42.66, 96.40% in HeLa at the concentration of 50, $100\;{\mu}g/ml$, respectively.

Inhibition of human breast carcinoma by BLC (Sargassum fulvellum) and BLC/HEN Egg in vitro and in vivo

  • Jo, Eun-Hye;Cho, Sung-Dae;Ahn, Nam-Shik;Jung, Ji-Won;Yang, Se-Ran;Park, Joon-Suk;Hwang, Jae-Woong;Lee, Sung-Hoon;Park, Jung-Ran;Kim, Sun-Jung;Park, Hyun-Kyung;Lee, Yong-Soon;Kang, Kyung-Sun
    • Korean Journal of Veterinary Research
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    • v.45 no.1
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    • pp.85-91
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    • 2005
  • Much of the interest on the chemopreventive properties of herbs and plants has been raised, whereas little is regarding to anti-tumor effect of farming and aquatic products. In the present study, the anti-tumor effect of hot-water extract of a seaweed, BLC (Sargassum fulvellum) and BLC/HEN egg was investigated using MCF-7 cells in vitro and in vivo systems. We found that the BLC extract and BLC/HEN egg inhibited cell proliferation in a dose-dependent manner, which might be mediated through up-regulation of p53. Furthermore, this test compound can directly induce apoptosis in MCF-7 cells, which might be mediated through up-regulation of a pro-apoptotic Bax protein and down-regulation of a anti-apoptotic Bcl-2 protein, not by immune system. Nude mice bearing established breast tumors (with exogenous estradiol) were treated with BLC extract and BLC/HEN egg. Treatment BLC extract and BLC/HEN egg caused a 42% and 71% inhibition of tumor growth, respectively. Both agents caused a significant inhibition of volume and weight growth of estrogen independent human breast tumors established from MCF-7 cells. Our results suggested that BLC extract and BLC/HEN egg have the efficacious effect of human breast cancer not only in vitro but also in vivo.