• Journal of Nutrition and Health
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• 제39권4호
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• pp.347-356
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• 2006

It is reported that a fermented soybean food, Doenjang, has srong antimutagenic and cytotoxic effect on cancer cells. This study investigated the effect of Chungkookjang, another traditional popular Korean soybean fermented food, on growth of cancer cells: HL-60, SNU-638 and MCF-7, and also its in vivo antitumorigenic effect in DMBA-induced mammary tumor rat model. For the in vitro study, Chungkookjang and steamed soybeans were extracted with ethanol and sequentially fractioned with 5 kinds of solvents differing in grades of polarity such as hexane, dichloromethane, ethylacetate, butanol and water. Almost all Chungkookjang extracts significantly inhibited the growth of HL-60 (human leukemic cancer cell), SNU-638 (human gastric cancer cell) and MCF-7 (human breast cancer cell) when compared to steamed soybean extracts. Butanol fraction of Chungkookjang extract especially showed a remarkable inhibitory effect in all the three kinds of cancer cells. To induce a mammary gland tumor, DMBA (50 mg/BW) was administered to 50 day-old female rats and followed by Chungkookjang or steamed soybean supplemented diets. Freezedried Chungkookjang powder (20% of diet in wet weight) was added to AIN-93G based diet for the Chungkookjang group of rats. Likewise, steamed soybean powder containing equal protein content to that of Chungkookjang powder was supplemented to soybean group of rats. At 13 weeks later, the mammary tumor incidence, average tumor number and tumor weight a rat were lower in Chungkookjang group compared to the control or soybean group. In conclusion, Chungkookjang showed a strong inhibitory effect on cancer cell growth in vitro, as well as a more preventive effect against chemically induced mammary tumorigenesis in vivo, while steamed soybeans did not. Therefore, these results suggest that Chungkookjang acquire its anticancer activity through the fermentation process.

• 미생물학회지
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• 제42권1호
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• pp.47-53
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• 2006

한국 토양에서 방선균주를 분리하고 화학 분류 및 16S rDNA 염기서열을 통하여 Streptomyces 속 균주임을 알아내고 Streptomyces sp. AO-0511로 명명하였다. 이 균주가 생산하는 herbimycin A 및 dihydroherbimycin A의 몇 가지 이화학적 성질과 생물 활성을 측정하였다. 두 물질은 모두 산성 조건에서 안정성을 나타냈으며, dihydroherbimycin A는 herbimycin A에 비해 상대적으로 높은 열 안정성을 지니며 극성 또한 높은 물질로서 TLC 상의 Rf간이 낮았다. Herbimycin A와 dihydroherbimycin A는 모두 Bacillus subtilis ATCC 6633 및 Micrococcus luteus ATCC 9341에 대하여 약한 저해 활성을 나타내었고, 다른 미생물에 대해서는 저해 활성을 나타내지 앓았다. 항암 활성에 있어서 두 물질은 폐암 세포인 AS49세포와 백혈병 세포인 HL-60세포에 대해서 강력한 중식 저해 활성을 나타내었다. L5178Y및 P388세포를 사용하여 세포 독성을 측정하였다. 그 결과 두 물질은 대조 물질인 camptothecin에 비해서 항암 활성을 가지면서도 비교적 안전한 물질임을 알려 주고 있다.

• Journal of Oral Medicine and Pain
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• 제20권1호
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• pp.53-65
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• 1995

The growth and synthetic activities of fibroblasts are regulated by cytokines and growth factors derived from activated inflammatory cells. Stimulatory effect of low level laser (LLL) radiation on wound healing seems to be in part due to direct stimulatory action on cell proliferation and synthetic activities of fibroblasts. Also indirect stimulatory effect on the fibroblast function through inflammatory or immune cells is another possible mechanism of biostimulatory action of LLL. This study was performed to determine the growth rate of human gingival fibroblasts obtained biopsy and culture, fibroblast cell line, and immune cell line by using $[^3H]-$ thymidine incorporation test. And gene expression pattern was also analyzed by using the DNA probe such as Hsp70, IL-1$\beta$, MIP-1$\alpha$ and actin cDNA. Proliferation rate of gingival fibroblast was increased by LLL irradiation, but no more effect was added by LPS or IL-1$\beta$ pretreatment Enhanced Hsp70 gene expression was found from gingival fibroblasts and fibroblast cell line COS by LLL irradiation., which was not more increased by LPS or IL-1$\beta$ pretreatment. LLL-irradiated promyelcytic cell line HL-60 and macrophage cell line RAW264.7 showed significant stimulatory effect of proliferation rate when compared with respective control. However there were no changes in growth rate of other immune cell tested in this study, such as B cell line WR19n.l and 230, helper T cell line Jurkat and Hut78, cytolytic T cell line CTLL-r8. By LLL-irradiation Hsp70 gene expression was increased in RAW246.7 and HL-60, not in CTLL-R8. And IL-1$\beta$ and MIP-1$\alpha$ gene expression were induced only from LLL-irradiated RAW264.7. These results led us to presume that LLL radiation may affect to the immune cells, especially to macrophage, through which it might promote wound healing process.

• Toxicological Research
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• 제26권1호
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• pp.21-28
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• 2010

As the frequency and the intensity of so called Asian dust (AD) events have increased, public concerns about the adverse health effects has spiked sharply over the last two decades. Despite the recent reports on the correlation between AD events and the risk for cardiovascular and respiratory disease, the nature of the toxicity and the degree of the risk are yet largely unknown. In the present study, we investigated the effects of the dichloromethane extract of AD (AD-X) and that of urban dust (NAD-X) collected during a non-AD period on gene expression in HL-60 cells using Illumina Sentrix HumanRef-8 Expression BeadChips. Global changes in gene expression were analyzed after 24 h of incubation with 50 or 100 ${\mu}g$/ml AD-X and NAD-X. By one-way analysis of variance (p < 0.05) and Benjamini-Hochberg multiple testing correction for false discovery rate of the results, 573 and 297 genes were identified as AD-X- and NAD-X-responsive, respectively. The genes were classified into three groups by Venn diagram analysis of their expression profile, i.e., 290 AD-X-specific, 14 NAD-X-specific, and 283 overlapping genes. Quantitative realtime PCR confirmed the changes in the expression levels of the selected genes. The expression patterns of five genes, namely SORL1, RABEPK, DDIT4, AZU1, and NUDT1 differed significantly between the two groups. Following rigorous validation process, these genes may provide information in developing biomarker for AD exposure.

• Archives of Pharmacal Research
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• 제24권2호
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• pp.144-149
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• 2001

N-acetylsphingosine (C2-ceramide) is a synthetic water-soluble ceramide mimicking the activity of natural ceramides. By fixing chiral conformation on carbon numbers 2 and 3 in the ceramide structure, four chiral C2-ceramides naming d-erythro-, I-erythro-, d-threo-and 1-three C2-ceramide were synthesized. We have investigated the chiral effects of these C2-ceramides on the sphingolipid metabolism, particularly on both the sphingolipid bio- synthetic pathway and on the degradation pathway. In both HL-60 and U937 cells, the chiral C2-ceramide ($10{\mu}\textrm{m}$) showed sphingosine accumulation monitored fluoromatrically by a high performance liquid chromatographic separation of the sphingoid bases. Most importantly, in HL-60 cells, l-erythro C2-ceramide induced a 50 fold increase in sphingosine as compared to the control, while l-threo C2-ceramide exhibited a minimal 7-fold in-crease. In contrast, sphinganine, another sphingoid base, showed less accumulation by any chiral C2-ceramide tested under the same conditions. These results suggested that chiral C2-ceramide primarilyacts on the sphingolipid degradation pathway rather than on the sphingolipid biosynthetic route. The strong $C_0/G_1$ phase arrest in the cell cycle by treatment of I-erythro C2-ceramide indicates that the blockade of the sphingolipid degradation pathway might be concomitantly involved in the dysfunction of the cell cycle. On the other hand, the fact that all chiral C2-ceramides tested failed to inhibit the activity of sphingosine kinase acting on the removal of sphingosine by producing sphingosine-1 -phosphate demonstrates that chiral C2- ceramides may increase sphingosine by activating various ceramidases by which natural ceramides are divided into sphingosine and free fatty acids. However, the precise steps involved in this interaction are still unknown.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.820-823
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• 2002

The diethylet er fraction from the leaves extract of Ligularia fischeri var. spiciformis (Compositae) was subjected to silica gel column chromatography and yielded three new terpenoids named spiciformisin a (1), spiciformisin b (3), and monocyclosqualene (2). Acyclic diterpenes, spiciformisin a and -b, were established as 3,7,11,15-tetramethyl-1,3(20)-hexadecadiene and 3,7,11,15-tetramethyl-1,3,6,10,14-hexadecapentaene (IUPAC), respectively. A monocyclic triterpene, monocyclosqualene, were determined as [3,8,12,16,16-pentamethyl-(3,7,11,15-hexadecatetraenyl)]-3,3,5-trimethyl-1-cyclohexene. The structures were determined on the basis of NMR and MS analysis. Spiciformicin b showed potent cytotoxicity ($IC_{50},{\;}<9.7{;\}{\mu\textrm{g}}/ml$ against HL-60) in contrast to no cytotoxicity ($IC_{50},{\;}>200{\;}}{\mu\textrm{g}}/ml against HL-60 cells) of spiciformicin a with a cis-conjugated dienyl diexomethylene.

• Journal of Photoscience
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• 제9권2호
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• pp.518-520
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• 2002

Photodynamic therapy (PDT) is a treatment modality based on photochemical reaction and the resultant cytotoxic reactive oxygen species. The platelet thrombus formation leading to stasis observed in vivo during PDT is called vascular shut down (VSD) effect. To investigate the mechanism of the VSD effect, we observed Human Umblical Vein Endothelial Cell (HUVEC) injury induced by photochemical reaction. We observed cell retraction and blebbing after PDT. It seems that the injury was not fetal and only morphological change. Then, the cytoplasm was stained by Calcein-AM and subendothelial area was evaluated from fluorescence microscopy. The rate of subendothelial area after PDT increased significantly. Second, we investigated interaction between neutrophils and HUVEC. Human promyelocytic leukemia cells (HL-60) were differentiated into neutrophil by incubation with all-trans retinoic acid. Calcein-AM labeled neutrophil adhesion to HUVEC was evaluated from fluorescence microscopy. PDT-induced neutrophil adhesion to HUVEC depended more on the exposure of subendothlial area than on neutrophil activation. This result suggests that there is a certain interaction between neutrophil and HUVEC during PDT.

• The Korean Journal of Physiology and Pharmacology
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• 제14권6호
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• pp.441-447
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• 2010

B13, a ceramide analogue, is a ceramidase inhibitor and induces apoptosis to give potent anticancer activity. A series of thiourea B13 analogues was evaluated for their in vitro cytotoxic activities against human renal cancer Caki-2 and leukemic cancer HL-60 in the MTT assay. Some compounds (12, 15, and 16) showed stronger cytotoxicity than B13 and C6-ceramide against both tumor cell lines, and compound (12) gave the most potent activity with $IC_{50}$ values of 36 and $9\;{\mu}M$, respectively. Molecular modeling of thiourea B13 analogues was carried out by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). We obtained highly reliable and predictive CoMSIA models with cross-validated $q^2$ values of 0.707 and 0.753 and CoMSIA contour maps to show the structural requirements for potent activity. These data suggest that the amide group of B13 could be replaced by thiourea, that the stereochemistry of 1,3-propandiol may not be essential for activity and that long alkyl chains increase cytotoxicity.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.145-146
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• 2001

There are increasing evidences that L-ascorbic acid (LAA) is selectively toxic to some types of tumors at physiological concentrations as a prooxidant, rather than antioxidant. However, the mechanism by which LAA initiates cellular signaling toward cell death is still unclear. Therefore, to determine whether LAA might be useful for the treatment of human acute promyelocytic leukemia (APL), HL-60 cells, the effects of LAA on proliferation, redox system, MAPK and induction of apoptotic cascades were investigated.(omitted)

• The Korean Journal of Physiology and Pharmacology
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• 제17권3호
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• pp.237-243
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• 2013

B13 is a ceramide analogue and apoptosis inducer with potent cytotoxic activity. A series of arylpropyl sulfonamide analogues of B13 were evaluated for their cytotoxicity using MTT assays in prostate cancer PC-3 and leukemia HL-60 cell lines. Some compounds (4, 9, 13, 14, 15, and 20) showed stronger activities than B13 in both tumor cell lines, and compound (15) gave the most potent activity with $IC_{50}$ values of 29.2 and 20.7 ${\mu}M$, for PC-3and HL-60 cells, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed to build highly reliable and predictive CoMSIA models with cross-validated $q^2$ values of 0.816 and 0.702, respectively. Our results suggest that long alkyl chains and a 1R, 2R configuration of the propyl group are important for the cytotoxic activities of arylpropyl sulfonamides. Moreover, the introduction of small hydrophobic groups in the phenyl ring and sulfonamide group could increase biological activity.