• Clinical and Experimental Pediatrics
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• 제58권6호
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• pp.199-205
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• 2015

Severe aplastic anemia (SAA) is a life-threatening disorder for which allogeneic hematopoietic stem cell transplantation (HSCT) is the current available curative treatment. HSCT from matched sibling donors (MSDs) is the preferred therapy for children with acquired SAA. For patients who lack MSDs, immunosuppressive therapy (IST) is widely accepted as a first-line treatment before considering HCT from an unrelated donor (URD). Given the recent progress in HSCT using URDs for childhood SAA, well-matched URDs became a realistic alternative for pediatric patients who have no suitable related donors and who are refractory to IST. However, it is quite challenging to treat patients with refractory SAA who lack suitable related or URDs. Even though haploidentical HSCT from genetically mismatched family members seemed to be an attractive procedure with the amazing benefit of readily available donors for most patients, early attempts were disappointing because of refractory graft-versus-host disease (GVHD) and excessively high transplant-related mortality. Recent advances with effective ex vivo depletion of T cells or unmanipulated in vivo regulation of T cells, better supportive care, and optimal conditioning regimens have significantly improved the outcome of haploidentical transplant. Besides considerable progress in the treatment of malignant diseases, recent emerging evidences for haploidentical HSCT in SAA has provided additional therapeutic options for patients with refractory diseases. Further improvements to decrease the rates of graft failure, GVHD, and infectious complications will facilitate the emergence of haploidentical HSCT as a front-line therapy for treating acquired SAA in children and adolescents who have no suitably matched donors.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.81-81
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• 2003

The present study was taken to examine the inhibitory effect of extracts of Scytosiphon lomentaria, a marine alga growing in Jeju Island, on the growth of cancer cells and to develop an anti-cancer agent using components of S. lomemtaria. The effect was observed by the measurement of metabolic activity using colorimetric 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. In results, crude extract of this alga markedly inhibited the growth of leukemia cell lines such as HL-60 and KG-1, but could scarcely inhibit the growth of normal cells (HEL299) and adenocarcinoma cells (SNU-16 and HCT-I5). When HL-60 cells were treated with the extract, DNA fragmentation and the increase of proportion of sub-G1 hypodiploid cells were observed. Therefore, the inhibitory effect of S. lomemtaria on the growth of HL-60 cells seems to arise from the induction of apoptosis. In order to understand the mechanism of apoptosis inducton by S. lomemtaria, we examined the changes of Bcl-2 and Bax expression. The extract reduced Bcl-2, an anti-apoptotic protein, but increased Bax, a pro-apoptotic protein in a dose-dependent manner. When we examined the activation of caspase-3, an effector of apoptosis, the expression of active form(19 kDa) of caspase-3 was increased and the increase of their activities was demonstrated by the cleavage of poly(ADP-ribose)polymerase, a substrate of caspase-3, to 85 kDa. The results indicate that extract of S. lomentaria induces the apoptosis of HL-60 cells via the down-regulation of Bc1-2 and the activation of caspases.

• Toxicological Research
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• 제28권1호
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• pp.33-38
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• 2012

In this study, we investigated the effect of methanolic extract isolated from the root of Lycoris aurea (LA) on the growth of cancer cells and the tube formation activity of endothelial cells. Various cancer cells were treated with LA at doses of 0.3, 1, 3, 10 or 30 ${\mu}g/ml$ and LA significantly suppressed the growth of several cancer cell lines, including ACHN, HCT-15, K-562, MCF-7, PC-3 and SK-OV-3, in a dose-dependent manner. We also found that LA induced cell cycle arrest at G2/M phase in ACHN renal cell adenocarcinoma cells. Further study demonstrated that LA concentration-dependently inhibited the tube formation, which is a widely used in vitro model of reorganization stage of angiogenesis, in human umbilical vein endothelial cells. Collectively, these results show that LA inhibits the growth of cancer cells and tube formation of endothelial cells and the growth-inhibitory effect of LA might be mediated, at least in part, by blocking cell cycle progression.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.396-403
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• 2017

Under normal, non-stressed conditions, intracellular p53 is continually ubiquitinated by MDM2 and targeted for degradation. However, in response to severe genotoxic stress, p53 protein levels are markedly increased and apoptotic cell death is triggered. Inhibiting the ubiquitination of p53 under conditions where DNA damage has occurred is therefore crucial for preventing the development of cancer, because if cells with severely damaged genomes are not removed from the population, uncontrolled growth can result. However, questions remain about the cellular mechanisms underlying the regulation of p53 stability. In this study, we show that p53-inducible gene 3 (PIG3), which is a transcriptional target of p53, regulates p53 stability. Overexpression of PIG3 stabilized both endogenous and transfected wild-type p53, whereas a knockdown of PIG3 lead to a reduction in both endogenous and UV-induced p53 levels in p53-proficient human cancer cells. Using both in vivo and in vitro ubiquitination assays, we found that PIG3 suppressed both ubiquitination- and MDM2-dependent proteasomal degradation of p53. Notably, we demonstrate that PIG3 interacts directly with MDM2 and promoted MDM2 ubiquitination. Moreover, elimination of endogenous PIG3 in p53-proficient HCT116 cells decreased p53 phosphorylation in response to UV irradiation. These results suggest an important role for PIG3 in regulating intracellular p53 levels through the inhibition of p53 ubiquitination.

• 생약학회지
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• 제34권4호통권135호
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• pp.308-313
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• 2003

A bioassay-guided fractionation of the stem bark extract of Eucommia ulmoides Oliver (Eucommiaceae) led to the isolation of three iridoid constituents, genipin (1), geniposide (3), geniposidic acid (4) as well as $({\pm})-guaiacylglycerol$ (2) and fatty acid mixtures as active ingredients of the extract responsible for the antitumoral property. The EtOAc soluble part and BuOH soluble part of the extract demonstrated a potent inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon) in vitro, whereas the remaining water soluble part exhibited a poor inhibition. The intensive investigation of the EtOAc soluble part and BuOH soluble part of the extract yielded genipin, guaiacylglycerol, geniposide, geniposidic acid and large amounts of fatty acid mixtures as active components.

• Natural Product Sciences
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• 제18권4호
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• pp.239-243
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• 2012

Mushrooms have a long history of use in traditional medicine, and hundreds of novel constituents in mushrooms with miraculous biological properties have been identified recently. Although diverse effects for medicinal use of mushrooms such as anticancer activity are proven, their reversal activities of drug resistance in cancer cells was rarely reported so far. In the search for novel medicinal use of mushrooms, we tested the multidrug resistance (MDR) reversal activities of diverse mushrooms collected from Korea. Among, the mushroom extracts tested, Cantharellus cibarius (M02) and Russula emetica (M12) revealed MDR reversal activities of paclitaxel in the P-glycoprotein (Pgp)-positive HCT15 and MES-SA/dX5 cancer cells, but not in the Pgp-negative A549 and MES-SA cancer cells. In addition, these mushrooms also enhanced the cytotoxicity of doxorubicin, another well-kwown Pgp-associated anticancer drug against MES-SA/DX5 cells, but not against MES-SA cells. Meanwhile, the cytotoxicity of cisplatin, a well-known Pgp-non-associated anticancer drug, was not affected by the mushrooms all the cells tested. From these results, we suspected that some ingredients of M02 and M12 have Pgp-associated MDR reversal activities.

• 한국식품조리과학회지
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• 제18권3호
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• pp.300-308
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• 2002

The purpose of this study was to investigate the effect of chloroform(CHC1$_3$) fraction of Alisma canaliculatum All. Braun et Bouche(Ac) with selenium(Se) on the plasma glucose and lipid levels in streptozotocin(STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into five groups. The normal and diabetic rats were separated into four groups: the STZ-control group, the Ac group, the Ac-Se group and the Se group. Diabetes was induced in the male rats by an injection of STZ into the tail vein at a dose of 45 mg/kg. The CHCl$_3$fraction of Ac(250 mg/kg) was administered orally for 14 days. The supplementation was achieved with the AIN-93 recommended diet by adding 2 mg/kg diet of selenium as Na$_2$SeO$_3$. which was prepared freshly everyday. The body weight, hematocrit(Hct), glucose, insulin, cholesterol, HDL-cholesterol, triglyceride(TG) and free fatty acids(FFA) concentrations in plasma were measured. The aminotransferase activities were also analyzed. The changes of body weight in the experimental groups were not significantly different from that of the STZ-control group, but diabetes hyperphagia accompanied changes with body weight loss in Ac-Se group. The levels of Plasma cholesterol were not significantly different among the experimental groups. The concentrations of FFA in the Ac-Se group increased significantly compared with the STZ-control group. The effect of Se alone significantly increased aspartate aminotransferase activity and alanine aminotransferase activity. The results showed that the treatment of CHCl$_3$fraction of Ac in combination with Se has no synergistic effect. There was a tendency for the plasma glucose levels to decrease when Se was administered into diabetic rats. Supplementation of Se in diabetic rats did not elicit a significant increase in plasma insulin levels and exhibited hypotriglyceridemic effect.

• 한국자원식물학회지
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• 제30권6호
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• pp.640-646
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• 2017

In this study, we elucidated anti-cancer activity and potential molecular mechanism of 70% ethanol extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) (TR-E70) against human colorectal cancer cells. Anti-cell proliferative effect of TR-E70 was evaluated by MTT assay. The effect of TR-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. TR-E70 suppressed the proliferation of human colorectal cancer cell lines, HCT116 and SW480. Although TR-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by TR-E70 more dramatically occurred than that of cyclin D1 mRNA. Cyclin D1 downregulation by TR-E70 was attenuated in presence of MG132. In addition, TR-E70 phosphorylated threonine-286 (T286) of cyclin D1. TR-E70-mediated cyclin D1 degradation was blocked in presence of LiCl as an inhibitor $GSK3{\beta}$ but not PD98059 as an ERK1/2 inhibitor and SB203580 as a p38 inhibitor. Our results suggest that TR-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through $GSK3{\beta}$-dependent cyclin D1 degradation. From these findings, TR-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

• 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.

• 대한수의학회지
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• 제34권4호
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• pp.833-842
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• 1994

To elucidate the protective effects of Lactobacillus acidophilus-fermented milk against cadmium toxicity, the effects of administration of L acidophilus-fermented milk on hematological values and histopathological changes in cadmium-treated rats were investigated. The experimental rats were divided into 2 groups that were consisted of the one group administered with cadmium alone, and the other group administered with cadmium mixed with the fermented milk. Each group was orally administered with different doses of cadmium such as $1.7{\mu}g/g$ bw/day, $3.4{\mu}g/g$ bw/day, $6.8{\mu}g/g$ bw/day, and $13.6{\mu}g/g$ bw/day, respectively, for 1 to 8 weeks. Hematological values and enzyme activities, histopathological changes of kidney tissues were examined for the experimental groups. The values of RBC, WBC, and Hb in the groups administered with cadmium mixed with the fermented milk showed no significant differences to those of the groups administered with cadmium alone, but Hct showed significant reducing values. The activities of glutamic oxaloacetic transaminase(GOT) and glutamic pyruvic transaminase (GPT) in serum were significantly reduced than those of the groups administered with cadmium alone, at the low dose of cadmium treated groups. But alkaline phophatase(ALP) and lactate dehydorgenase(LDH) were significantly reduced at the high dose of cadmium treated groups. In histopathological study, a severe acute tubular necrosis of the convoluted tubules and distalation of tubules were showed in the groups administered with cadmium alone, but the kidney tissues of the groups administered with cadmium mixed with the fermented milk were similar to those of the normal group. In conclusion, the above results would suggest that L acidophilus-fermented milk has reducing effects on cadmium toxicity, at the low dose of cadmium administration.