• Archives of Pharmacal Research
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• 제26권1호
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• pp.9-14
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• 2003

For probing the importance of planarity of imidazolidinone motif of 4-phenyl-1-(benzenesulfonyl)imidazolidinones 1 for their cytotoxicity, 4-phenyl-2-(benzoyl)[1,2,5]thiadiazolidine-1,1-dioxide (2a), 4-phenyl-2-(p-toluoyl)[1,2,5]thiadiazolidine-1,1-dioxide (2b), 4-phenyl-2-(phenylcarbamoyl)[1,2,5]thiadiazolidine-1,1-dioxide (3a), and 4-phenyl-2-(p-tolylcarbamoyl)[1,2,5]thiadiazolidine-1,1-dioxide (3b) were prepared along with their regioisomers (5a, 5b, 9a, 9b) and their cytotoxicity were measured against human lung carcinoma (A549), human colon carcinoma (COLO205), human ovarian cancer (SK-OV-3), human leukemic cancer (K562), and murine colon adenocarcinoma (Colon26) cell lines in vitro. All compounds prepared do not show any activity against all five cancer cell lines unlike 1. Compounds 1 possess planarity of imidazolidinone, especially in sulfonylurea moiety ($-SO_2$NHCONH-). However compounds 2 and 3 have nonplanar 5-membered ring, [1,2,5]thiadiazolidine-1,1-dioxides. Such structural differentiation might result in the loss of activity. Therefore the inactivity of 2 and 3 could also be an indication for the necessity of planarity of imidazolidinone ring of 1 for their cytotoxic activity.

• Toxicological Research
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• 제21권4호
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• pp.355-360
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• 2005

Epidemiological and laboratory studies provide insight into the anti-carcinogenic potential of garlic and its constituent compounds. Garlic is appealing as an anti-carcinogenic agent due to its ability to induce apoptosis in vitro. Diallyl disulfide (DADS) is one of the major components of garlic that used to determine inhibition of cell proliferation and induced apoptosis in human colon cell lines. In this study, human colorectal cancer cell lines (LOVO, HCT-116, SW-480) were exposed to DADS. The inhibitory effects of DADS dose level more than $50\;{\mu}M$ in the cell viability of all cell lines. Cell growth activity inhibits of human colon cancer cell lines. The inhibitory effects of DADS dose level more than $25\~50\;{\mu}M$ in the cell growth using MTT assay. We found that DADS may have the apoptosis action (chromatin condensation, DNA fragmentation) using DAPI staining and increased the expression of caspase-3 at the dose level more than $100\;{\mu}M$, decreased the expression level of $\beta-catenin$ at dose dependent in the western blotting. We suggest that DADS may have a potential candidate as cancer chemopreventive agents.

• 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.

• 생약학회지
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• 제37권3호
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• pp.130-135
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• 2006

The present study describes the preliminary evaluation of the cytotoxic activity of the extracts from Inula japonica. I. japonica was extracted with methanol, ethanol, acetone, and water, and then cytotoxic activity of these extracts were evaluated. The cytotoxic activity of each extract was assessed by the MTT-dye reduction assay. Both ethanol and acetone extracts from I. japonica showed the cytotoxic activity against the HT-29 human colon cancer cells. Furthermore, the ethanol extract was fractionated with n-hexane, diethyl ether, ethyl acetate, and water according to degree of Polarity, The diethyl ether fraction showed the highest cytotoxic activity against HT-29 cells, but the other fractions showed low cytotokic activity. In addition, diethyl ether layer also showed the cytotoxic activity against various tumor cells, such as human colon carcinoma SW620, human cervix adenocarcinoma HeLa, and human breast adenocarcinoma MCF-7 cells as well as HT-29 cells. These studies support that extracts of I. japonica may be a potential candidate as possible chemotherapeutic agent against human cancer.

• 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.

• 산업식품공학
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• 제15권1호
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• pp.64-69
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• 2011

본 실험에서는 대장암 세포 HT-29의 증식을 억제하고 세포 사멸을 유도하는 천연소재 발굴을 목적으로, 오미자(Schizandra chinensis Baillon) 열수 추출물을 이용하여 인체대장암 세포 HT-29의증식에 미치는 영향을 확인하였다. 오미자 열수 추출물이 HT-29 대장암 세포의 apoptosis 유도 효과 및 기전에 미치는 영향을 분자생물학적 방법으로 실험하여 다음과 같은 결론을 얻었다. MTT assay를 통해 인체 대장암세포 HT-29는 오미자 시료농도 0, 1.0, 2.0, 4.0 mg/mL에서 암세포 사멸농도가 각각 0%, 10%, 70%, 88%를 나타내었다. 대장암세포에 오미자 추출물을 처리하고 cell cycle 분석 결과, 시료농도 의존적으로 sub-G1기가 증가하였고, G0/G1기는 감소되는 것을 통해, apoptosis가 일어나 세포 증식을 저해하는 것으로 확인되었다. 대장암세포 핵의 형태학적 변화를 보면, 오미자 추출물 처리 시 농도 의존적으로 세포수가 감소되는 것이 뚜렷이 관찰되었고 cell shrinking, chromatin condensation등 apototic body 등과 같은 형태학적 변화들이 뚜렷하게 관찰되었다. RT- PCR을 통한 유전자 발현은, 오미자 추출물 농도 의존적으로 p53 유전자 발현이 증가되는 것을 통해 대장암세포의 증식억제를 확인할 수 있었다. In vitro 실험에서 오미자 열수추출물이 대장암세포의 성장을 저해하는 효과가 있음을 확인하였으며, 오미자 추출물에 함유된 활성 본체 규명 및 apoptosis를 유도하는 작용기작에 관한 연구가 수행중이다.

• 약학회지
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• 제48권3호
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• pp.189-196
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• 2004

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) playa key role in tumor invasion and metastasis. As an inhibitor of MMP-2, TIMP-2 is known to block both the invasive and metastatic behavior of cancer cells, and decrease tumor growth activity. We performed this study to investigate the effects of TIMP-2 over-expression induced by retroviral mediated gene transfer in vitro and in vivo. The human colon cancer cell line SW480 was transfected with the retroviral vector encoding TIMP-2. The effects of TIMP-2 over-expression were analyzed by invasion assay and gelatinase activity test in colon cancer cells and tumorigencity in nude mice. In evaluation of the transfection efficiency of the retroviral vector encoding TIMP-2 in colon cancer cells, we confirmed up-regulation of TIMP-2 expression dependent on the time of cell culture. In addition, inhibition of MMP-2 expression in SW480/TIMP-2 was shown by gelatin zymography. In the in vitro invasion assay SW480/TIMP-2 inhibited the invasiveness on matrigel coated with collagen. To determine whether TIMP-2 can modulate in vivo tumorigenicity and metastasis, SW480/TIMP-2 cells were injected subcutaneously in nude mice. The tumor mass formation of SW480/TIMP-2 cells in nude mice was markedly decreased compared to nontransfected cancer cells. These results showed that colon cancer cells transfected with the retroviral vector encoding TIMP-2 inhibits the invasiveness in vitro and tumorigenicity in vivo.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.320-327
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• 2016

Columbianadin (CBN), a natural coumarin from Angelica decursiva (Umbelliferae), is known to have various biological activities including anti-inflammatory and anti-cancer effects. In this study, the anti-proliferative mechanism of actions mediated by CBN was investigated in HCT-116 human colon cancer cells. CBN effectively suppressed the growth of colon cancer cells. Low concentration (up to $25{\mu}M$) of CBN induced apoptosis, and high concentration ($50{\mu}M$) of CBN induced necroptosis. The induction of apoptosis by CBN was correlated with the modulation of caspase-9, caspase-3, Bax, Bcl-2, Bim and Bid, and the induction of necroptosis was related with RIP-3, and caspase-8. In addition, CBN induced the accumulation of ROS and imbalance in the intracellular antioxidant enzymes such as SOD-1, SOD-2, catalase and GPx-1. These findings demonstrate that CBN has the potential to be a candidate in the development of anti-cancer agent derived from natural products.

• Animal cells and systems
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• 제15권1호
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• pp.9-17
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• 2011

Colorectal cancer is the third leading cause of cancer-related death in Western countries. Chemotherapeutic agents with different mechanisms of action have shown an increase in cure rates. In the present study, we investigated the effect of a combination of low concentration of paclitaxel (taxol, 5 nM) and topoisomerase 1 inhibitor camptothecin (CPT) on HCT116 colon cancer cells. Although the viability of cells treated with taxol alone was similar to that of control cells, sequential treatment with taxol and CPT exhibited high cytotoxicity. However, the opposite sequence of treatment did not exert cytotoxic effects on HCT116 cells. This enhanced cytotoxicity of the sequential combination therapy was the result of mitotic arrest, which increased the level of $p21^{Cip1/WAF1}$ through the p38 mitogen-activated protein kinase (MAPK) pathway. Knockdown by $p21^{Cip1/WAF1}$ siRNA or treatment with a p38 inhibitor reduced the viability of cells sequentially exposed to taxol and CPT. Taken together, a low taxol concentration in combination with CPT induced mitotic arrest in HCT116 cells, leading to synergistic cell death through enhanced expression of $p21^{Cip1/WAF1}$ and p38 MAPK pathway. Therefore, taxol could playa role as a sensitizer of CPT in colon cancer cells.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1987년도 Proceedings of Korea-Japan Panax Ginseng Symposium 1987 Seoul Korea
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• pp.29-37
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• 1987

This study was devised to observe the cytotoxlc activities of petroleum-ether extract of Panax ginseng root(crude Gx) and its partially purified fraction from silicon acid column chromatography(7:3 CX) against sarcoma-180(5-180) and Walker carcinosarcoma 256(Walker 256) in vivo, and murine leukemic lymphocytes(L1210) and human rectal cancer cell(HRT-18) and human colon cancer cells(HT-29 and HCT-48) in vitro . Each cell-line was cultured in medium containing serial concentrations of the crude Gx or 7:3 Gx in vitro. A highly lipid soluble compound in the extract of Panax ginseng root was cytocidal to murine leukemic cells and human colon and rectal cancer cells in vitro In the meantime, ginseng saponin derivatives did not cytotoxic effects at its corresponding concentration. The growth rates of the cancer cells in medium containing ginseng extracts were inhibited gradually to a significant degree roughly in proportion to the increase of the extract concentration. The cytotoxic activity of 7:3 Gx was about 3 times more potent than that of crude Gx, one unit of cytotoxic activity against L121f cells being equivalent to 2.54$\mu\textrm{g}$ and 0.88 $\mu\textrm{g}$ for the crude Gx and 7:3 Gx, respectively. The Rf value of the active compound on silica -gel thin layer chromatography with petroleum-ether/ethyl ether/acetic acid mixture (90:10:1, v/v/v) as a developing solvent was 0.23. The survival times of mice inoculated with S-180 cells were extended about 1.5 to 2 times by the 7:3 Gx treatment compared with their control group. The significantly decreased hemoglobin values of rats after inoculation with Walker 256 were recovered to normal range by oral administration of the crude Gx. The synthetic levels of protein, DNA and RNA in human colon and rectal cancer cells were significantly diminished by treatment with the crude Gx, which can explain a part of the origin of its anticancer activity.