• 대한암한의학회지
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• 제15권1호
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• pp.29-36
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• 2010

The anti-metastatic activity of water extract of Samguikoeuitang (WSGKE) consisting of Ginseng Radix, Angelicae Radix, Sophora flavescens and Coicis Semenwas examined. Ethanol extract of Samguikoeuitang (ESGKE) showed significant cytotoxicity against colon 26-M3.1 carcinoma cells, while WSGEK did not. However, WSGKE significantly increased the production of IL-6 and IL-12 in thioglycollate-induced macrophages from Balb/c mice, whereas ESGKE did not. WSGKE significantly increased natural killer (NK) cell cytotoxicity against effecter YAC-1 cells in an Effecter cells/Target ratio dependent manner. Also, WSGKE significantly suppressed lung metastasis after i.v. injection of colon26-M3.1 carcinoma cells. Inhibitory effect of WSGKE on lung metastasis totally abolished in NK cells-deficient mice by treatment with anti-asialo GM1 serum. In addition, the combination treatment of cisplatin and WSGKE (100 ${\mu}g$/mouse) prolonged the lifespan of mice inoculated by colon26-M3.1 cell. These findings suggest that WSGKE can inhibit lung metastasis and prolong life span via immunological enhancement as a Biological Response Modifier.

• 한국식품영양과학회지
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• 제28권5호
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• pp.1107-1112
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• 1999

We investigated the inhibitory effects of phytol and methyl 11,14,17 eicosatrienoic acid (methyl ETA, n 3, 20 : 3) separated from perilla leaves on the growth of human cancer cells. Phytol inhibited significantly the growth of HT 29 human colon cancer cells, MG 63 osteosarcoma cells and AZ 521 gastric cancer cells. Although the activity of methyl ETA was lower than that of phytol, it was also observed to have the inhibitory effect on three human cancer cell lines. Furthermore, the DNA synthesis of the MG 63 osteosarcoma cells was markedly decreased by the addition of the phytol and methyl ETA. These results suggest that phytol and methyl ETA identified from the perilla leaves may play a role on the growth inhibition of the human cancer cells.

• Natural Product Sciences
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• 제6권4호
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• pp.183-188
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• 2000

In order to discover novel potent antitumor agents, methanolic extracts of approximately 180 herbal medicines were prepared and primarily evaluated for cytotoxic activity in cultured human lung (A549) and colon (Col 2) cancer cells. As a result, 17 natural product extracts were found to be active in the criteria of $IC_{50}$<$20\;{\mu}g/ml$. Especially, the extracts of Aristolochia debilis, Cynanchum ascyrifolium, Cynanchum paniculatum, Daphne genkwa, Euphorbia lathyris, Ipomoea hederacea, Magnolia officinalis, Melia azedarach var. japonica, Solanum nigrum, Thuja orientalis, and Trichosanthes kirilowii showed a strong cytotoxic potential. The flower extract of Daphne genkwa was more selective cytotoxic activity against lung cancer cells $(IC_{50};\;0.2\;{\mu}g/ml)$ compared to colon cancer cells $(IC_{50}>20\;{\mu}g/ml)$. In addition, based on the cytotoxic potential of the root extract of Cynanchum paniculatum, the further fractionation of methylene chloride partition with silica gel column chromatography was performed. Several subfractions were considered to be active, and thus indicating that further studies for the identification of active principles from these fractions might be warranted.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3113-3121
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• 2014

Colorectal cancer remains one of the most common types of cancer and a leading cause of cancer death worldwide. In this study, we aimed to investigate effects of DuP-697, an irreversible selective inhibitor of COX-2 on colorectal cancer cells alone and in combination with a promising new multi-targeted kinase inhibitor E7080. The HT29 colorectal cancer cell line was used. Real time cell analysis (xCELLigence system) was conducted to determine effects on colorectal cell proliferation, angiogenesis was assessed with a chorioallantoic membrane model and apoptosis was determined with annexin V staining. We found that DuP-697 alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. For the antiproliferative effect the half maximum inhibition concentration ($IC_{50}$) was $4.28{\times}10^{-8}mol/L$. Antiangiogenic scores were 1.2, 0.8 and 0.5 for 100, 10 and 1 nmol/L DuP-697 concentrations, respectively. We detected apoptosis in 52% of HT29 colorectal cancer cells after administration of 100 nmol/L DuP-697. Also in combination with the thyrosine kinase inhibitor E7080 strong antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells were observed. This study indicates that DuP-697 may be a promising agent in the treatment of colorectal cancer. Additionally the increased effects observed in the combination with thyrosine kinase inhibitor give the possibility to use lower doses of DuP-697 and E7080 which can avoid and/or minimize side effects.

• 생명과학회지
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• 제17권5호
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• pp.671-677
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• 2007

발효 및 비발효 차가버섯 수용성 추출물이 정상 세포주 NIH3T3 mouse normal fibroblast cell 및 인체 종양 세포주 AGS human gastric cancer cell(위암), HCT-15 human colon cancer cell(대장암), Hep3B human hepatoma cancer cell(간암), MCF-7 human breast cancer cell(유방암), HeLa human cervical cancer cell(자궁경부암)에서 MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay 방법에 의한 세포 증식 억제와 암세포 증식억제의 기전 연구의 일환으로 apoptosis가 일어날 때 나타나는 DNA fragmentation을 agarose gel electrophoresis 방법으로 검토하였다. 인체 종양 세포주의 생육저해 효과가 발효 차가버섯 추출물이 비발효 차가버섯 추출물보다 강한 것으로 나타났다. 그러나 동일한 실험조건하에서 마우스 정상 세포주 NIH3T3은 80% 이상의 생존율을 나타내어 정상 세포주에는 큰 영향을 미치지 않는 것으로 나타났다. 특히, 발효 및 비발효 차가버섯 추출물에서 본 실험에 사용한 세포주 중에서 대장암 세포주 HCT-15에 대해 가장 세포 증식 억제효과가 뛰어났으며, 이러한 효과는 첨가 농도 의존적 이였다. 발효 및 비발효 차가버섯 추출물에 의한 암세포 증식억제가 기전 연구로 apoptosis가 일어날 때 나타나는 DNA fragmentation을 세포로부터 genomic DNA를 분리하여 agarose gel electrophoresis 방법으로 조사한 결과, 정상세포인 NIH3T3 세포는 DNA fragmentation이 거의 일어나지 않아 세포 생존율 결과와 유사한 경향을 보였으나, 특히 대장암 세포주인 HCT-15에서는 발효 차가버섯뿐만 아니라 비발효 차가버섯 추출물에서도 DNA fragmentation이 많이 일어나는 것이 관찰되어 암세포 증식억제 효과가 높다는 결과를 뒷받침 해주고 있다.

• 통합자연과학논문집
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• 제16권3호
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• pp.81-95
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• 2023

Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

• Archives of Pharmacal Research
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• 제29권3호
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• pp.209-212
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• 2006

We investigated the effect of protein extract of Asterina pectinifera on the activity of 4 enzymes that may playa role in adenocarcinoma of the colon: quinone reductase (QR), glutathione Stransferase (GST), ornithine decarboxylase (ODC), and cyclooxygenase (COX)-2. QR and GST activity increased in HT-29 human colon adenocarcinoma cells increased that had been exposed to 4 concentrations of the protein extract (80, 160, 200, and $240{\mu}g/mL$). Additionally, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ODC activity decreased significantly in cells exposed to the extract in concentrations of $160{\mu}g/mL$ (p<0.05), $200{\mu}g/mL$ (p<0.005), and $240{\mu}g/mL$ (p<0.005). TPA-induced COX-2 activity also decreased in cells exposed to extract concentrations of 10, 20, 40, and $60{\mu}g/mL$. COX-2 expression was also inhibited in cells exposed to this extract. These results suggest that this protein extract of A pectinifera has chemopreventive activity in HT-29 human colon adenocarcinoma cells, and therefore, may have the potential to function as a chemopreventive agent in human colorectal cancer.

• Biomolecules & Therapeutics
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• 제23권2호
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• pp.134-140
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• 2015

Conjugated linoleic acids (CLA) are a family of isomers of linoleic acid. CLA increases growth arrest and apoptosis of human colorectal cancer cells through an isomer-specific manner. ATF3 belongs to the ATF/CREB family of transcription factors and is associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which t10, c12-CLA stimulates ATF3 expression and apoptosis in human colorectal cancer cells. t10, c12-CLA increased an apoptosis in human colorectal cancer cells in dose dependent manner. t10, c12-CLA induced ATF3 mRNA and luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by t10, c12-CLA is located between -147 and -1850 of ATF3 promoter. mRNA stability of ATF3 was not affected by t10, c12-CLA treatment. t10, c12-CLA increases $GSK3{\beta}$ expression and suppresses IGF-1-stimulated phosphorylation of Akt. The knockdown of ATF3 suppressed expression of $GSK3{\beta}$ and NAG-1 and PARP cleavage. The results suggest that t10, c12-CLA induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.

• 공업화학
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• 제25권4호
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• pp.363-367
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• 2014

본 연구에서는 큰실말 부산물의 추출 조건(HCl, $H_2SO_4$, NaOH, $Na_2CO_3$, $Na_2EDTA$)에 따른 식이섬유 함량을 조사하였다. 또한 큰실말 부산물로부터 분리한 식이섬유의 총 폴리페놀과 플라보노이드양을 측정하고 HT-29 대장암 세포에서의 증식 억제를 통한 항암효과를 확인하였다. 1.5% $Na_2EDTA$와 0.05 N HCl이 큰실말 부산물로부터 가용성 식이섬유를 추출하는데 효과적이었으며 추출 시간과 온도도 가용성 식이섬유의 추출수율에 영향을 주었다. 큰실말 부산물 식이섬유의 총 폴리페놀과 플라보노이드 함량은 1% NaOH 추출물에서 가장 높게 측정되었다(총 폴리페놀 $34.4{\pm}0.055$ mg gallic acid/g dry basis, 총 플라보노이드 $34.7{\pm}0.023$ mg naringin/g extract dry basis). 또한 DPPH 라디칼 소거능 측정에서도 1% NaOH 추출물에서 가장 높은 항산화 효과를 보였다. 대장암 세포주의 세포 생존율 측정 결과, D.W.와 0.05 N HCl 및 0.5% $Na_2CO_3$ 추출물에서 농도의존적 세포 증식 억제를 보였다. 이들 결과는 큰실말 부산물로부터 분리한 가용성 식이섬유가 항산화 및 대장암에서의 항암효과에 중요한 기능이 있음을 시사한다.

• BMB Reports
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• 제43권11호
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• pp.750-755
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• 2010

Crude Orostachys japonicus polysaccharide extract (OJP) was prepared by hot steam extraction. Polysaccharides (OJPI) were separated from OJP by gel filtration chromatography and phenol-sulfuric acid assay. The average molecular weight of the OJPI was 30-50 kDa. The anti-proliferative effect of OJPI on HT-29 human colon cancer cells was investigated via morphology study, cell viability assay, apoptosis assay, cell cycle analysis, and cDNA microarray. OJPI inhibited proliferation and growth of HT29 cells and also stimulated apoptosis in a dose- and time-dependent manner. In cell cycle analysis, treatment with OJPI resulted in a marked increase of cells in the G0 (sub G1) and G2/M phases. To screen for genes involved in the induction of cell cycle arrest and apoptosis, the gene expression profiles of HT-29 cells treated with OJPI were examined by cDNA microarray, revealing that a number of genes were up- or down-regulated by OJPI. Whereas several genes involved in anti-apoptosis, cell proliferation and growth, and cell cycle regulation were down-regulated, expression levels of several genes involved in apoptosis, tumor suppression, and other signal transduction events were up-regulated. These results suggest that OJPI inhibits the growth of HT-29 human colon cancer cells by various apoptosis-aiding activities as well as apoptosis itself. Therefore, OJPI deserve further development as an effective agent exhibiting anticancer activity.