• Archives of Pharmacal Research
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• 제29권4호
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• pp.318-322
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• 2006

Many quaternary ammonium salts are incompletely absorbed after their oral administration and may also be actively secreted into the intestine. However, the underlying mechanism(s) that control the transport of these cations across the intestinal epithelium is not well understood. In this study, the mechanism of absorption of quaternary ammonium salts was investigated using Caco-2 cell monolayers, a human colon carcinoma cell line. Tributylmethylammonium (TBuMA) was used as a model quaternary ammonium salts. When TBuMA was administrated at a dose of 13.3 imole/kg via iv and oral routes, the AUC values were $783.7{\pm}43.6\;and\;249.1{\pm}28.0{\mu}mole\;min/L$ for iv and oral administration, indicating a lower oral bioavailability of TBuMA $(35.6\%)$. The apparent permeability across Caco-2 monolayers from the basal to the apical side was 1.3 times (p<0.05) greater than that from the apical to the basal side, indicating a net secretion of TBuMA in the intestine. This secretion appeared to be responsible for the low oral bioavailability of the compound, probably mediated by p-gp (p-glycoprotein) located in the apical membrane. In addition, the uptake of TBuMA by the apical membrane showed a $Na^+$ dependency. Thus, TBuMA appears to absorbed via a $Na^+$ dependent carrier and is then secreted via p-gp related carriers.

• The Korean Journal of Physiology and Pharmacology
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• 제5권2호
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• pp.177-181
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• 2001

Recently, nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to be useful in the chemoprevention of colon cancer. To investigate whether indomethacin, an NSAIDs, induces apoptosis and thus assess the possibility of its application in the chemoprevention of human lung cancer, we have performed MTT assay, TUNEL assay, DAPI staining, and flow cytometric analysis using human lung carcinoma cell line NCI-H1299. Through morphological and biochemical analyses, it was demonstrated that NCI-H1299 cells treated with indomethacin (0.5 mM) exhibit classical apoptotic features. These results suggest that indomethacin induces apoptosis in NCI-H1299 cells and that NSAIDs, including indomethacin, may be a useful tool for the chemoprevention of human lung cancer.

• Archives of Pharmacal Research
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• 제27권8호
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• pp.829-833
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• 2004

The bioactivity-guided fractionation of the methylene chloride extract of the sclerotium of Poria cocos led to the isolation of (S)-(＋)-turmerone (1), ergosterol peroxide (2), polyporenic acid C (3), dehydropachymic acid (4), pachymic acid (5), and tumulosic acid (6). Compounds 4-6 exhibited moderate cytotoxicities, with $IC_{50}$ values of 20.5, 29.1, and $10.4{\;}\mu\textrm{m}$, respectively, against a human colon carcinoma cell line. However, 3-6 not only showed inhibitory activities as potent as etoposide used as a positive control on DNA topoisomerase II (36.1, 36.2, 43.9 and 66.7％ inhibition at a concentration of $20{\;}\mu\textrm{m}$, respectively), but also inhibition of DNA topoisomerase I (55.8, 60.7, 43.5, and 83.3％ inhibition at a concentration of $100{\;}\mu\textrm{m}$, respec-tively).

• Biomolecules & Therapeutics
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• 제7권2호
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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.

• BMB Reports
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• 제53권7호
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• pp.385-390
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• 2020

Inflammatory Bowel Disease is caused by an acute or chronic dysfunction of the mucosal inflammatory system in the intestinal tract. In line with the results of our previous study, wherein we found that the PKCα-LSD1-NF-κB signaling plays a critical role in the prolonged activation of the inflammatory response, we aimed to investigate the effect of signaling on colitis in the present study. Lsd1 S112A knock-in (Lsd1^SA/SA) mice, harboring a deficiency in phosphorylation by PKCα, exhibited less severe colitis symptoms and a relatively intact colonic epithelial lining in dextran sulfate sodium (DSS)-induced colitis models. Additionally, a reduction in pro-inflammatory gene expression and immune cell recruitment into damaged colon tissues in Lsd1^SA/SA mice was observed upon DSS administration. Furthermore, LSD1 inhibition alleviated colitis symptoms and reduced colonic inflammatory responses. Both LSD1 phosphorylation and its activity jointly play a role in the progression of DSS-induced colitis. Therefore, the inhibition of LSD1 activity could potentially protect against the colonic inflammatory response.

• Journal of Ginseng Research
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• 제17권1호
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• pp.52-60
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• 1993

Panax ginseng has been extensively used in the traditional oriental medicine as a restorative, tonic and Prophylactic agent. Recently, several reports regarding to anticancer effects of Panax ginseng has accumulated. These studies emphasized the fact that the anticancer activities might be due to a glycoside group called ginsenoside or pan.u saponin which has a water soluble characteristic. However, the authors and collaborates demonstrated that a highly lipid soluble component in extract of Panax ginseng roots contains a considerable cytotoxic activities against marine leukemic cells (L1210, P388) and human censer cells (HRT-18, HT-29, HCT48). This study was devised to observe the cytotoxic activities of Petroleum-ether extract of Panax giuseng roots (crude GBD and its Partially Purified fraction from silicic acid column chromatography (7 : 3 GX) against sarcoma-180 (5-180) and Walker carcinosar- coma 256 (Walker 256) in vivo, and murine leukemic Lymphocytes (L1210) and human rectal cancer cells (HRT-18) and human colon cancer cells (HT-29 and HCT48) in vitro. Each cell-line was cultured in medium containing serial concentration 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 have 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 L1210 cells being equivalent to 2.54 Ug and 058 Ug for the crude GX and 7 : 3 GX, respectively. The Ri 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 so lvent was 053. While, the Panaxydol and Panaxynol as active compounds were purified from Petroleum-ether extract of Panax ginseng root by Drs. Ahn and Kim, and author found out that the one unit of cytotoxic activity of the Panaxydol and Panaxynol against L1210 cells being equivalent to 056 Ug and 0.3918 respectively. 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 Gt 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.

• 한국식품영양과학회지
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• 제42권5호
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• pp.675-681
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• 2013

기능성 고추장을 제조할 목적으로 브로콜리잎 분말을 첨가하여 고추장을 제조한 후 80% 메탄올, 80% 에탄올, 물로 추출하여 총페놀 함량과 항산화 및 항암활성을 측정하여 재래식 고추장 및 개량식 고추장과 비교하였다. 총페놀 함량은 80% 메탄올과 80% 에탄올 추출물에서 브로콜리 고추장이 각각 524.2와 541.9 mg GAE/100 g으로 재래식 고추장의 431.0과 499.9 mg GAE/100 g보다 각각 22%와 8% 높았다. DPPH radical 소거능은 80% 메탄올 추출물에서는 브로콜리 고추장이 재래식 고추장보다 1.6배 높았으나, 80% 에탄올 추출물에서는 브로콜리 고추장과 재래식 고추장이 비슷하였다. 활성산소 흡수능력은 80% 메탄올과 80% 에탄올 추출물에서 브로콜리 고추장이 재래식 고추장보다 높았으나 유의적인 차이를 나타내지 않았으며 개량식 고추장보다는 각각 55%와 23% 높았다. ACE 저해 활성은 80% 메탄올 추출물에서 브로콜리 고추장은 재래식 고추장과는 유사하였으나 개량식 고추장보다는 2.6배 높았다. 항암활성은 브로콜리 고추장의 80% 에탄올 추출물인 경우 대장암 세포주(HT-29)와 폐암 세포주(NCI-H1229)에서 각각 10.7과 18.3%의 생장 저해효과를 나타내었다. 따라서 브로콜리잎의 건조분말을 첨가하여 재래식 방법으로 제조한 고추장은 총페놀 함량이 높으며, 재래식 고추장이나 공장식 고추장보다 다소 높은 항산화 활성과 암세포 성장 저해효과를 나타내어 브로콜리 분말의 첨가에 의해 고추장의 기능성이 향상되었다.

• 한국식품영양학회지
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• 제31권6호
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• pp.836-843
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• 2018

The objective of this study was to determine the effect of high hydrostatic pressure (HHP) treatment on proliferation of human cancer cell lines (MCF-7, HCT-116, PC-3 and AGS) of crude soyasaponin extracts in germinated black soybean. Black soybean was germinated and subjected to HHP, followed by preparation of crude soyasaponin extracts. Cell treatments done with extracts less than $400{\mu}g/mL$ concentrations had no significant effect on 3T3-L1 adipocyte cell viability. The inhibitory effect of crude soyasaponin extracts with germination periods and applied pressure on breast cancer cell (MCF-7), human colon cancer cell (HCT-116), human gastriccancer cell (AGS) and prostate cancer cell (PC-3) growth were investigated using MTT assay. The highest anti-proliferation of human cancer cell line of crude soyasaponin extracts was observed at 150 MPa treatment after germination for 4 days (150 MPa-Day 4). The cell viability on MCF-7, HCT-116, PC-3 and AGS cell lines of crude soyasaponin extract in 150 MPa-Day4 was 48.82%, 57.37%, 39.89% and 23.94% at $400{\mu}g/mL$, respectively. These results suggest that soyasaponin extracts from black soybean subjected to HHP after germination may mediate physiological activity.

• Journal of Nutrition and Health
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• 제23권2호
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• pp.135-147
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• 1990

본 연구는 유기용매로 추출한 마늘의 항암성 성분을 in vitro에서 흰생쥐의 백혈병성 임퐈모 세포인 L$_{1210}$과 P${388} 및 인체 직장암 세포인 HRT-18과 인체 결장암 세포인 HCT-48과 HT-29 또한 invivo에서 흰쥐 복수 육종암세포인 sarcoma-180세포를 대상으로 선별 시험한 것이다. S-180을 제외한 각 암세포는 in vitro에서 마늘추출물을 농도별로 첨가한 배양액에서 배양시험하였다. 암세포의 증식억제효과는 마늘의 석유에텔추출물이 알코올추출물보다 높았다. 마늘의 지용성 성분은 in vitro에서 흰생쥐의 백혈병성 임퐈모 세포, 인체 직장암 및 결장암 세포에 대해 항암효과물을 나타내었다. 각 암세포의 증식률은 첨가한 마늘추출물의 농도가 증가할수록 감소한 영향을 보였다. Petroleum ether/ethyl ether/acetic acid(90:10:1, v/v/v)의 전개용매로 사용한 TCL에서 분리한 유효한 활성성분의 Rf치는 0.18이었고, 정제하지 않은 마늘추출물보다 L$_{1210}$세포에 대해 2.3배 높은 활성을 나타냈다. S-180 암세포로 유발한 흰생쥐에 마늘 추출물을 투여한 군이 투여하지 않은 군보다 생존 기간이 1.5내지 2배 가량 연장효과를 보였다. S-180 암세포를 함유하고 있는 흰 생쥐에 마늘추출물(3ug/head)을 복강내 주사하고 3시간 후에 관찰한 결과 S-180 암세포의 뚜렷한 형태변화를 관찰하였다.

• IMMUNE NETWORK
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• 제1권3호
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• pp.221-229
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• 2001

Background: Inactivation of tumor suppressor genes is believed to be important in the development of many human malignancies. Recently, several lines of evidence have indicated that the wild type p53 gene located at 17p13.3, may function as a tumor suppressor gene and that a mutant p53 gene could promote transformation by inactivating normal p53 function in a dominant negative fashion. These broad spectrum of p53 mutation in human cancers provide that mutant p53 and their protein may be potential targets of tumor diagnostic and therapeutic interventions. Method: Colony formation was performed to investigate growth suppressional ability. p53 expression pattern was examined by western blot and p53-mediated transactivation ability was assessed by CAT activity. SNU C2A cells were observed in apoptotic aspects induced by etoposide and $H_2O_2$ treatment, detecting sensitivity on agent, DNA fragmentation through agarose gel, chromatin condensation by fluorescence microscope, and cell cycle distribution by FACS. Result: 1) p53 mutant his179arg ($histidine{\rightarrow}arginine$) detected in SNU C2A cells lost transcriptional activity and growth suppression ability, showing dominant negative effect on its wild type p53. 2) Etoposide-treated SNU C2A cells induced apoptosis, exhibiting dramatic reduction of cell growth, DNA fragmentation, nuclear condensation formation of apoptotic body and increment of sub-G1 cell fraction. 3) Etoposide and $H_2O_2$-treated SNU C2A cells have no high increase of p53 expression and overexpressed p53 protein changed localization, from cytoplasm to nucleus. Also, p53-mediated transcriptional activity was increased by agents-treatment. Conclusion: SNU C2A cells coexpress wild-type and mutant p53 protein induced apoptosis in the condition on DNA damage, through localizational shift from cytoplasm to nucleus of p53 protein rather than the induction of p53 protein. SNU C2A cells derived mutant p53 his179arg abrogated both the growth supression ability and transactivational activity, showing inhibition effect on transcriptional activity of wild type p53, but did not repress the activity of wild type p53 in SNU C2A cells owing to dominant activity of wild type. These cell condition may provide new gene therapeutic implications leading effective antiproliferation of cell when mutant and wild-type p53 protein were co-expressed in cell.