• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3395-3402
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• 2015

Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

• 한국식품영양과학회지
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• 제41권1호
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• pp.14-19
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• 2012

발아기간에 따른 발아 벼 추출물의 항산화성분, 항산화활성 및 암세포주 성장억제효과를 살펴보았다. 발아는 0, 2, 4, 6 및 8일 동안 진행하였으며, 발아 후 70% 에탄올로 추출물을 제조하였다. 발아가 진행됨에 따라 항산화성분 및 항산화활성은 2~4일까지는 증가하였다가 그 이후에는 감소하였다. 총 폴리페놀 함량은 발아 4일차에서 4.05 mg/g으로 가장 높았으며, DPPH 라디칼 소거능은 0, 2, 4, 6 및 8일차 각각 29.25, 34.82, 31.17, 26.27 및 18.51%로 발아 2일차에 가장 높았으며, 총 항산화력은 발아기간별로 각각 3.05, 3.17, 3.84, 2.43 및 2.167 mg AA eq/100 g으로 발아 4일차에서 가장 높게 나타났다. 환원력 또한 발아 4일차에 1.25로 가장 높게 나타났다. 암세포주 성장억제효과는 위암세포주(AGS) 보다 대장암세포주(HCT-116)에서 높게 나타났다. 이상의 결과로부터 생리활성 증가를 위해서 벼를 발아시킬 경우3~4일이 적당한 것으로 판단되며, 추후 새로운 물질의 생성과 생리활성 성분들에 대한 연구가 더 진행되어야 할 것으로 판단된다.

• 한국약용작물학회지
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• 제26권2호
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• pp.141-147
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• 2018

Background: Astilbe chinensis (Maxim.) Franch. Et Savat. is a plant belonging to Saxifragaceae family and contains various active ingredients including astilbin and bergenin. It has been used as a traditional Korean medicine to improve fever, pain, and cough. Recently, a number of Korean medical resources have been studied for cancer and inflammation treatment, but A. chinensis (Maxim.) Franch. Et Savat. has not yet been investigated. Consequently, this study investigated the inhibitory effect of ethanol extracts from A. chinensis (Maxim.) Franch. Et Savat. (ARE) on oxidative stress and colorectal cancer using RAW264.7 and the human colorectal cancer cell line HCT-116. Methods and Results: In total, $500{\mu}g/m{\ell}$ ARE reduced cell viability by $38.96{\pm}1.32%$, and increased caspase-3 activity by $133.08{\pm}3.41%$ in HCT-116 cells. Moreover, TUNEL signaling and the early apoptosis ratio ($34.56{\pm}1.67%$) increased by $500{\mu}g/m{\ell}$ ARE treatment. $H_2O_2$-induced oxidative stress and cell death were diminished by $500{\mu}g/m{\ell}$ ARE treatment through decreasing ROS (reactive oxygen species). Conclusions: The inhibitory effects of ARE against human colorectal cancer cells is mediated by apoptosis and caspase-3 activation, and $H_2O_2$-induced ROS generation and cell death are decreased by ARE treatment in RAW264.7 cells. However, further study is required to explore how ARE treatment is involved in the signaling pathway to decrease ROS.

• 한국약용작물학회지
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• 제26권1호
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• pp.19-25
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• 2018

Background: Inula japonica Thunb. is a plant belonging to the family compositae. Inulae flos (flower of I. britannica var. chinensis Regal.) is the dried flower of I. japonica Thunb. and contains various flavonoids (patulitrin, nepitrin and kaempferol), which have been utilized in traditional oriental medicine to treat nausea, phlegm, and coughs. However, ethanol extract of I. britannica (IJE) has not been previously studied for its use in cancer treatment, and its effects on oxidative stress, or inflammation. Thus, the present study investigated the anti-oxidant, anti-inflammatory, and anti-colorectal cancer effects of IJE using RAW264.7 and HCT-116 cells, which are human colorectal cancer cell line. Methods and Results: IJE contained flavonoids ($80.95{\pm}5.3mg/g$) and polyphenols ($310.53{\pm}10.6mg/g$). Moreover, it reduced lipopolysaccharide (LPS)-induced nitric oxide (NO) production and $H_2O_2$-induced oxidative stress by decreasing reactive oxygen species (ROS) levels. Additionally, the $500{\mu}g/m{\ell}$ IJE treatment increased caspase-3 activity and apoptotic cell death in HCT-116 cells. Conclusions: These results demonstrate that the anti-cancer effect of IJE against human colorectal cancer cells involves caspase-3 activation and apoptotic cell death. IJE also inhibited LPS-induced NO production, and $H_2O_2$-induced oxidative stress in RAW264.7 cells. However, further studies are required to explore how IJE treatment regulates signal transduction in NO and ROS production.

• Bulletin of the Korean Chemical Society
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• 제29권7호
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• pp.1303-1310
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• 2008

Inhibitors of farnesyltransferase (FT), a key enzyme in the post-translational modifications of Ras proteins, have been extensively studied as novel anticancer agents in the preclinical stages, some of which are currently in clinical development. Previously, it has been reported that a novel FT inhibitor LB42907 inhibits Ras farnesylation in the nanomolar range in vitro. The aim of this study was to assess the antitumor efficacy of LB42907 in vitro and in vivo. Anchorage-independent growth of various human tumor cell lines was potently inhibited by treatment with LB42907, comparable to other FT inhibitors in clinical development. In the nude mouse, oral administration of LB42907 demonstrated potent antitumor activity in several human tumor xenograft models including bladder, lung and pancreas origin. Interestingly, significant tumor regression in EJ (bladder) and A549 (lung) xenografts was induced by LB42907 treatment. The effectiveness of LB42907 was also investigated in simultaneous combination with paclitaxel, vincristine, cisplatin or gemcitabine against NCI-H460, A549, and HCT116 cells in vitro using median-effect analysis. LB42907 markedly synergized with most anticancer drugs tested in this study in NCI-H460 cell. In contrast, LB42907 displayed antagonism or partial synergism with these drugs in A549 and HCT116 cells, depending on the class of combined drugs and/ or the level of cytotoxicity. Our results demonstrate that LB42907 is an effective antitumor agent in vitro and in vivo and combination of LB42907 with other chemotherapeutic drugs results in synergistic or antagonistic effects mainly in a cell line-dependent manner. Further preclinical study is warranted.

• 대한화학회지
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• 제56권6호
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• pp.679-691
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• 2012

New series of metal complexes of Co(II), Ni(II), Cu(II), Zn(II), Pd(II) and Pt(II) with 4-(p-chlorophenyl)-1-(pyridin-2-yl)thiosemicarbazide (HCPTS) have been synthesized and characterized by elemental analyses, magnetic moment, spectra (IR, UV-Vis, $^1H$ NMR, mass and ESR) and thermal studies. The IR data suggest different coordination modes for HCPTS which behaves as a monobasic bidentate with all metal ions except Cu(II) and Zn(II) which acts as a monobasic tridentate. Based on the electronic and magnetic studies, Co(II), Cu(II), Pd(II) and Pt(II) complexes have square - planner, Ni(II) has mixed stereochemistry (tetrahedral + square planar), while Zn(II) is tetrahedral. Molar conductance in DMF solution indicates the non-ionic nature of the complexes. The ESR spectra of solid copper(II) complex show $g_{\parallel}$ (2.2221) > $g_{\perp}$ (2.0899) > 2.0023 indicating square-planar structure and the presence of the unpaired electron in the $d_x2_{-y}2$ orbital with significant covalent bond character. The thermal stability and degradation kinetics of the ligand and its metal complexes were studied by TGA and DTA and the kinetic parameters were calculated using Coats-Redfern and Horowitz-Metzger methods. The complexes have more antibacterial activity against some bacteria than the free ligand. However, the ligand has high anticancer activities against HCT116 (human colon carcinoma cell line) and HEPG2 (human liver hepatocellular carcinoma cell line) compared with its complexes.

• BMB Reports
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• 제39권2호
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• pp.171-177
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• 2006

Nonsteroidal anti-inflammatory drugs such as indomethacin (IN) can exert anti-colorectal cancer (CRC) activity through cyclooxygenase independent mechanism, but the exactly biological mechanism is not completely known. Here we use proteomic tools to investigate the molecular mechanism of this action. First, nude mice bearing tumors derived from subcutaneous injection with human CRC cell line HCT116 were randomly allocated to groups treated with or without indomethacin. Later, tumor lumps were incised and then total proteins extracted. After separated with two-dimensional electrophoresis, thirty-one differently expressed spots were found between IN-treated and non-IN-treated groups, of which 25 spots decreased and 6 spots increased in abundance in IN-treated group. Through matrix-assisted laser desorption ionization time of flight mass spectrometry and then NCBInr and SWISS-PROT databases searching, 12 protein spots were finally identified including galectin-1, annexin A1, annexin IV, trancription factor BTF3A, calreticulin. Most of the identified proteins are correlated with tumor's biological prosperities of proliferation, invasion, apoptosis and immunity, or take part in cell's signal transduction. From above we thought that indomethacin can exert its effect on colorectal cancer through regulating several proteins' expression directly or indirectly. Further study of these proteins may be helpful in founding new targets of drugs for cancer chemotherapy.

• 한국작물학회지
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• 제57권4호
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• pp.353-358
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• 2012

본 연구에서는 검정찰옥수수 종실을 일반분쇄와 저온미세분쇄를 하여 입자크기에 따른 항산화 활성과 cytotoxicity를 평가하여 이용성 증진을 하고자 연구를 수행하였다. 본 연구의 결과를 요약하면 다음과 같다. 1. 분쇄 정도에 따른 평균값은 일반분쇄가 $473.7{\mu}m$, 저온미세분쇄 $17.2{\mu}m$이었으며 중간값은 $336.9{\mu}m$와 $13.4{\mu}m$를 나타내었다. 2. TEAC 활성 측정 결과 일반분쇄는 $3.87{\mu}mol$ TE/g로서 저온미세분쇄 $5.15{\mu}mol$ TE/g보다 낮은 활성을 보였다. FRAP 활성 측정에서는 저온미세분쇄가 $10.08{\mu}mol$ Fe(II)/g로 일반분쇄 $8.86{\mu}mol$ Fe(II)/g보다 높은 활성을 보였다 3. 간암 세포주(Hep-G2) 성장억제에 미치는 영향은 1 mg/ml 농도에서 검정찰옥수수 종실을 일반분쇄(31.48%)한 것보다 저온미세분쇄(27.41%)를 한 경우가 암세포 생장 억제 효과를 큰 것으로 나타났다. 4. 대장암 세포주인 HCT-116에서는 1 mg/ml에서 분쇄정도에 따라 큰 차이를 보이지 않았으며, 유방암 세포주(MCF-7)에서는 일반분쇄가 미세분쇄보다 높은 생장억제를 보였다.

• 한국작물학회지
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• 제58권1호
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• pp.20-27
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• 2013

고들빼기의 부위별 성분 및 생리활성 차이를 검토하고자 일반성분, 폴리페놀 및 플라보노이드 함량, 항산화성 및 항암성을 분석하였다. 고들빼기 식물체 부위별 조단백질과 조지방은 꽃, 잎, 줄기 뿌리 순으로 높았고 조섬유와 조회분은 줄기와 뿌리가 꽃과 잎보다 높은 것으로 나타났다. 고들빼기의 총 페놀 함량은 꽃($72.9\;mgkg^{-1}$)에서 가장 높게 나타났고, 그 다음은 잎, 줄기, 뿌리 순으로 나타났다. 총 플라보노이드 함량은 잎($23.3\;mgkg^{-1}$), 꽃, 줄기, 뿌리 순으로 나타났다. 고들빼기에서 DPPH(DPPH radical scavenging activity)법에 의한 항산화성은 농도와 비례하게 활성이 증가하는 양상을 합성 항산화제 Vitamin C와 BHT보다 낮은 활성이지만 뿌리, 잎, 꽃, 줄기 순으로 높은 활성을 보였다. MTT assay에 의한 세포독성 시험결과 뿌리 추출물이 폐암(Calu-6) ($IC_{50}=196.3\;mgkg^{-1}$)과 대장암 세포주(HCT-116) ($IC_{50}=623.6\;mgkg^{-1}$)에 대해서 가장 높은 활성을 보였다. 생리활성물질 함량과 그 활성은 고들빼기 부위별로 다르게 나타났으며 총 페놀 함량과 총 플라보노이드 함량은 생리활성과 낮은 연관성을 보였으나 항산화성과 항암활성간에는 높은 상관관계를 보인 것으로 나타났다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.2061-2068
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• 2015

Background: Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Materials and Methods: Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of $600mm^3$ to $700mm^3$. The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). Results: The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Conclusions: Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis.