• Title/Summary/Keyword: Colon Cancer

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Implications of NQO1 in cancer therapy

  • Oh, Eun-Taex;Park, Heon Joo
    • BMB Reports
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    • v.48 no.11
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    • pp.609-617
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    • 2015
  • NAD(P)H:quinone oxidoreductase (NQO1), an obligatory two-electron reductase, is a ubiquitous cytosolic enzyme that catalyzes the reduction of quinone substrates. The NQO1- mediated two-electron reduction of quinones can be either chemoprotection/detoxification or a chemotherapeutic response, depending on the target quinones. When toxic quinones are reduced by NQO1, they are conjugated with glutathione or glucuronic acid and excreted from the cells. Based on this protective effect of NQO1, the use of dietary compounds to induce the expression of NQO1 has emerged as a promising strategy for cancer prevention. On the other hand, NQO1-mediated two-electron reduction converts certain quinone compounds (such as mitomycin C, E09, RH1 and β-lapachone) to cytotoxic agents, leading to cell death. It has been known that NQO1 is expressed at high levels in numerous human cancers, including breast, colon, cervix, lung, and pancreas, as compared with normal tissues. This implies that tumors can be preferentially damaged relative to normal tissue by cytotoxic quinone drugs. Importantly, NQO1 has been shown to stabilize many proteins, including p53 and p33ING1b, by inhibiting their proteasomal degradation. This review will summarize the biological roles of NQO1 in cancer, with emphasis on recent findings and the potential of NQO1 as a therapeutic target for the cancer therapy.

Effects of Korean and Chinese Crataegi Fructrus on the Antioxidant Activity and Antiproliferation of Cancer Cells (한국산과 중국산 산사의 항산화 활성 및 암세포 증식 억제효과)

  • Park, Yonghyun;Lee, Hyun-Joo;Lee, Jae-Joon
    • The Korean Journal of Community Living Science
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    • v.26 no.1
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    • pp.103-113
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    • 2015
  • This study examines the effects of Korean Crataegi fructrus(KCF) and Chinese Crataegi fructrus(CCF) on the antioxidative activity and antiproliferation of human cancer cells(HCT-116 human colon, Hep G2 human liver, and A549 human lung cancer cells). The total polyphenol and flavonoid contents, and antioxidative index of the Crataegi fructrus ethanol extracts were significantly higher in KCF than in CCF. The DPPH radical-scavenging activity of the KCF ethanol extract was 82.26%(1000 ppm), and that of the CCF ethanol extract was 77.64%. Antiproliferation effects of 80% ethanol extracts of KCF and CCF on human cancer cells(HCT-116, Hep G2 and A549) increased in a dose-dependent manner. Inhibitory effects of KFC on HCT-116 and A549 cells were greater than those of CCF. The results suggest that ethanol extracts of Crataegi fructrus have antioxidative and hyperplasia inhibition effects on human cancer cells.

Anticancer Effects of Natural Medicinal Plant Extracts on Oral Carcinoma Cells (천연 약용식물 추출물의 구강상피세포암 세포주에 대한 항암효과)

  • 김정희;현진원;김여갑
    • Biomolecules & Therapeutics
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    • v.7 no.2
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    • pp.153-157
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    • 1999
  • The anticancer effect of medicinal plants against two oral carcinoma cells, A253 and SCC-25 were investigated in this study. Methanol extracts from 63 medicinal plants, which have anticancer activities against other cancers such as stomach, hepatocellular or colon carcinomas, were prepared and screened for their anti- oral cancer activity by using MTT assay. Thirty one samples showed anti-oral cancer activity against either cell line used, however, other 32 samples had no anti-oral cancer activity. Among these samples methanol extract of Caesalpinia sappan revealed the strongest anti-oral cancer activity. The $IC_{50}$/ values of this extract against A253 and SCC-25 cells were 16 and 25 $\mu$g/m1, respectively. Fractions of n-hexane, dichloromethane, ethylacetate, n-buthanol and water were prepared from methanol extracts of Caesalpinia sappan, Anthriscus sylvestris, Rhus japonica, Curcuma arowatica, Inula helenium, Sinoarnudinaria reticulata, and Polygonum cuspidatum, respectively. Among these 35 fractions the n-hexane fraction of Inula helenium showed the strongest anti-oral cancer activity, the $IC_{50}$/ value was 1.6$\pm$0.3 $\mu\textrm{g}$/ml. Ten other fractions showed $IC_{50}$/ values lower than 10 $\mu\textrm{g}$/ml.

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Influence of Depression on Cancer Metastasis (암환자의 우울이 전이발생에 미치는 영향)

  • Lee, Suk-Jeong;Kim, Joo-Hyung;Park, Young-Mi
    • Asian Oncology Nursing
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    • v.8 no.2
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    • pp.105-110
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    • 2008
  • Purpose: This study was a retrospective analysis with survey study which analyze influence of depression of patients with cancer on metastasis. Methods: The subjects of this research were 223 patients who underwent chemotherapy or are in follow-up management with stomach, colon, or breast cancer. The questionnaires were collected in 2002 and medical documents were reviewed 400 days after the first data collection. Subjects were divided according to the depression level into over-average group and under average group. Results: In survival analysis, metastasis occurred in 49 of 211 in 223 subjects for whom follow-up review was done after 400 days. The depression and anxiety level were higher in the group with metastasis than the other with no metastasis. As a result, it showed that the lower depression they have, the lesser the metastasis occurred. Conclusion: This research showed that patients who have higher level of depression, experienced higher risk for cancer metastasis. Nurses who take care of cancer patients are responsible for giving patients with positivity with intention to subside their depression.

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Clinical implications of the Hippo-YAP pathway in multiple cancer contexts

  • Kim, Han-Byul;Myung, Seung-Jae
    • BMB Reports
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    • v.51 no.3
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    • pp.119-125
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    • 2018
  • The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy. The analysis of YAP expressions can facilitate the identification of patients who respond better to an anti-cancer drug treatment comprising RAF-, MEK-, and EGFR-targeted inhibitors. The prominence of YAP for those aspects of cancer biology denotes that these factors are ideal targets for the development of anti-cancer medications. Therefore, our report strongly indicates that the YAP is of potential prognostic utility and druggability in various human cancers.

Role of Interventional Managements for Malignant Colorectal Obstruction (소화관 폐색을 동반한 대장암 환자에서 중재적 치료의 역할)

  • Eun Soo Kim
    • Journal of Digestive Cancer Research
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    • v.1 no.1
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    • pp.1-5
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    • 2013
  • Incidence of colorectal cancer has been increasing in Korea probably due to the westernized life style. Although the technical development of colonoscopy and introduction of screening examination has led to the detection of early colorectal cancer, considerable patients still have clinical symptoms of colorectal obstruction. Most of these patients are old and they have advances stage of cancer or severe co-morbidities. In addition, the emergency operation under poor preparation state of colon can lead to serious mortality or complications. Since the introduction of colorectal stent, there have been a large number of studies for recent 10 years. It seems that the role of colorectal stent in the palliative indication or bridge to surgery has been recognized. A well designed, randomized prospective study with long term data is necessary to support the role of colorectal stent in the malignant colorectal obstruction.

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The Relationship between F-18-FDG Uptake, Hexokinase Activity and Glut-1 Expression in Various Human Cancer Cell Lines (다양한 사람 종양세포주에서 F-18-FDG의 섭취와 Hexokinase 활성 및 Glut-1 발현과의 상관관계)

  • Kim, Bo-Kwang;Chung, June-Key;Lee, Yong-Jin;Choi, Yong-Woon;Jeong, Jae-Min;Lee, Dong-Soo;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.4
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    • pp.294-302
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    • 2000
  • Purpose: To investigate the mechanisms related to F-18-FDG uptake by tumors, F-18-FDG accumulation was compared with glucose transporter-1 (Glut-1) expression and hexokinase activity in various human cancer cell lines. Materials and Methods: Human colon cancer (SNU-C2A, SNU-C4, SNU-C5), hepatocellular carcinoma (SNU-387, SNU-423, SNU-449), lung cancer (NCI-H522, NCI-H358, NCI-H1299), uterine cervical cancer (HeLa, HeLa 229, HeLa S3) and brain tumor (A172, Hs 683) cell lines were used. After 24 hr incubation of $5{\times}10^5$ cells, 37 kBq F-18-FDG was added and the uptake by cells at 10 min was measured using a gamma counter. Hexokinase activity was measured by continuous spectrophotometric rate determination. To measure mitochondrial hexokinase activity, mitochondrial fraction was separated by a high speed centrifuge. Immunohistochemical staining of Glut-1 was performed, and graded as 0, 1, 2, or 3 according to expression. Results: There was difference among F-18-FDG uptake, total and mitochondrial hexokinase activity, and Glut-1 expression with different cancer cell lines. The correlations of F-18-FDG with total hexokinase and mitochondrial hexokinase activity were low (r=0.27 and 0.26, respectively). Glut-1 expression showed a good correlation with F-18-FDG uptake (p=0.81, p=0.0015). Previously, we reported no correlation of F-18-FDG uptake with hexokinase activity in colon cancer cell lines. Thus, when colon cancer cells were excluded, F-18-FDG uptake showed higher correlation with total hexokinase and mitochondrial hexokinase activity (r=0.81, p=0.0027 and r=0.81, p=0.0049, respectively). Conclusion: Both Glut-1 expression and hexokinase activity were contributing factors related to F-18-FDG accumulation in human cancer cell lines. The relative contribution of Glut-1 expression and hexokinase activity, however, was different among different cancer cell types.

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Physiological Activity of Alliin and Ethanol Extract from Korean Garlic (Allium Sativum, L.) (한국산 마늘로 부터 분리한 Alliin과 에탄올 추출물의 In Vitro계 생리 활성)

  • Lim, Seung-Woo;Kim, Tae-Hyeo
    • Korean Journal of Food Science and Technology
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    • v.29 no.2
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    • pp.348-354
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    • 1997
  • This study was designed to evaluate the effects of garlic extracts of various concentrations on the growth of various pathogens and human colon cancer cell lines in vitro. For antibacterial effects against microorganisms, minimal inhibition concentrations (MIC) of alliin were from 5,000 to 20,000 ppm. MIC of ethanol extract were from 1,250 to 10,000 ppm. For cytotoxic effect of alliin and ethanol extract against human colon cancer cell lines (HCT-15), the growth rates of the cancer cells in medium containing alliin and ethanol extract were inhibited gradually to a significant degree in proportion to the increase of these concentration. Morphology of HCT-15 cells in medium containing alliin and ethanol extract were seen to be shrinked and fragmented. The results show that the causes of the antibacterial and cytotoxic effect against a wide range are thermostable substances isolated by the ethanol.

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PRP4 Kinase Domain Loss Nullifies Drug Resistance and Epithelial-Mesenchymal Transition in Human Colorectal Carcinoma Cells

  • Ahmed, Muhammad Bilal;Islam, Salman Ul;Sonn, Jong Kyung;Lee, Young Sup
    • Molecules and Cells
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    • v.43 no.7
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    • pp.662-670
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    • 2020
  • We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using Gateway™ technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.

Cytotoxic Effects of Partially Purified Substances from Bacillus polyfermenticus SCD Supernatant toward a Variety of Tumor Cell tines

  • Chang, Kyung-Hoon;Park, Jun-Seok;Choi, Jae-Hoon;Kim, Cheon-Jei;Paik, Hyun-Dong
    • Food Science and Biotechnology
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    • v.16 no.1
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    • pp.163-166
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    • 2007
  • The cytotoxic effects of partially purified substances from Bacillus polylfermenticus SCD toward a variety tumor cell lines were studied. Cytotoxic activity was determined with regard to the A549 (human lung carcinoma), AGS (human stomach adenocarcinoma), DLD-1 (human colon adenocarcinoma), HEC-1-B (human uterus adenocarcinoma), SW-156 (human kidney carcinoma), and NIH/3T3 (murine normal fibroblast) cell lines using the MTT assay. Cytotoxic substances were partially purified through Diaion HP-20 columns and extracted with methanol or other organic solvents (n-hexane, chloroform, ethylacetate, and butanol). B. polyfermenticus SCD supernatant showed up to 60% inhibition of cell viability fer all five human cancer cell lines tested. When treated with 10 mg/mL of n-hexane, chloroform, ethylacetate, and butanol extract, HEC-1-B cells showed a 25,62,35, and 63% rate of inhibition respectively, and AGS cells showed a 72, 61, 44, and 67% rate of inhibition, respectively. At a concentration of 10 mg/mL, 100% methanol Diaion HP-20 extracts showed inhibition rates of 97.0% toward A-549 cells, 98.1% toward AGS cells, 81.6% toward DLD-1 cells, 83.5% toward HEC-1-B cells, and 92.7% toward SW-156 cells. These results indicate that partially purified fractions from B. polyfermenticus SCD have the potential to inhibit not only colon cancer cells, but also lung, stomach uterus, and kidney cancer cells. Further studies are needed to characterize the cytotoxic substances released in B. polyfermenticus SCD cultures.