• YAKHAK HOEJI
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• v.42 no.3
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• pp.248-256
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• 1998

We had already reported that we purified N-${\beta}$-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), a novel antibacterial substance from the immunized adult Sarcoph aga peregrina (Flesh fly). We found that the antibacterial activity of synthetic 5-S-GAD is equal to that of authentic 5-S-GAD without a specificity of antibacterial activity against Gram positive and Gram negative. Significant synergism was detected between 5-S-GAD and streptomycin against streptomycin resistant strain E.coli K12 594. It has an antitumor activity against several tumor cell lines at a concentration of $100{\mu}M$. However, no cytotoxic activity against murine macrophage was detected at a concentration of $500{\mu}M$. Furthermore, haemolytic activity against sheep erythrocytes was not detected at the same concentration. We suggest that the S-conjugation of glutathion with dihydroxyphenylalanine might be important to increase antibacterial activity of dihydroxyphenylalanme.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.6 no.1
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• pp.47-65
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• 2000

In order to investigate antitumor and immune response effect by Hyangsapyungwisan after Sarcoma-180 cells and methotrexate were treatred each other, the extract of Hyangsapyungwisan was orally administered to ICR mice for 14 days. To evaluate the effects of the Hyangsapyungwisan, 50% inhibition concentration($IC_{50}$), mean survival days, tumor weight for antitumor effects, hemagglutinin titer, hemolysin titer, rosette forming cells, natural killer cell activity and productivity of interleukin-2 for immune responses measured in ICR mice. The results were summarized as follows: 1. Mean survival time in Hyangsapyungwisan-treated group was slightly prolonged, as compared with control group(13.46%). 2. On the MTT assay, cell viability was significantly inhibited by $5{\mu}g/well,\;2.5{\mu}g/well,\;1.25{\mu}g/well,\;and\;0.625{\mu}g/well$ of Hyangsapyung-wisan concentration inhibited cell viability significantly. $IC_{50}$ for cell viability was $11.59{\mu}g/well$. 3. Tumor weight in Hyangsapyungwisan treated group was depressed, as compared with the control group(p<0.05). 4. Hemagglutinin titer in Hyangsapyungwisan-treated group was slightly increased with no significance, as compared with the control group. 5. Hemolysin titer in Hyangsapyungwisan-treated group was silightly increased, as compared with the control group(p<0.05). 6. Rosette forming cells in Hyangsapyungwisan-treated group was silightly increased, as compared with the control group(p<0.05). 7. Naural killer cell activity in Hyangsapyungwisan-treated group was significantly increased(p<0.05). 8. Production of interleukin-2 was significantly increased(p<0.05). According to the above results, Hyangsapygwisan had prominent antitumor effects, and enhance both cellular and humoral immunity in mice.

• Food Science of Animal Resources
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• v.23 no.1
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• pp.80-85
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• 2003

This study was carried out to investigate antimicrobial and antitumoral activities of Candida kefyr TFP7 isolated from Tibetan fermented milk Strains of TFP1∼10 were isolated from Tibetan fermented milk by agar diffusion method using potato dextrose agar(PDA). Antimicrobial activities were examined against 18 microorganisms of food-related bacteria, yeast, algae, fungi and actinomycetes isolated from soil. Antitumor activities were examined against 9 human tumor cell lines. Strains of TFP2∼10 showed strong antimicrobial activities against Micrococcus luteus ATCC l1880, and strains of TFP6∼10 to actinomycetes, Streptomyces murinus JCM 4333. In antitumor test, all isolated strains(TEP1∼10) showed the growth inhibition of SNU-5 and SW-534 by 60% and 70%, respectively. Among those, the strain TFP7 showed the most antitumor activity, which was 77.5% for SNU-5 and 76.5% for SW-534. The strain was identified as Candida kefyr by use of API 20C AUX kit and scanning electron micrograph.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.915-921
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• 2015

Context: In the last half century, discovering, developing and introducing of clinical agents from marine sources have seen great successes, with examples including the anti-cancer compound trabectedin. However, with increasing need for new anticancer drugs, further exploration for novel compounds from marine organism sources is strongly justified. Objective: The major aim of this study was to evaluate the antitumor and antioxidant potential of Sargassum tenerrimum J.Agardh (Sargassaceae) on Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Materials and Methods: An ethanol extract of S. tenerrimum (EEST) from whole algae was used to evaluate cytotoxicity followed by in vivo assessment of toxicity, using biochemical parameters including hepatic and non-hepatic enzymes. Antioxidant properties were examined in animals bearing EAC treated with daily oral administration of 100-300 mg/kg extract suspension. Results: Antitumor effects of EEST in EAC bearing mice was observed with LD50 1815 mg/kg. Parameters like body weight, tumor volume, packed cell volume, tumor cell count, mean survival time and increase in life span in animals in the EAC bearing animals treated with EEST 300 mg/kg was comparable with control group. Significant differences were also seen with changes in total protein content, hepatic enzymes contents, MDA level, and free radical scavenging enzymes in untreated vs. EEST treated group animals. Conclusions: Evaluation of antioxidant enzymes and hepatic enzymes in the EAC animal model treated with EEST exhibited similar effects as the positive control drug 5-flurouracil. S. tenerrimum extracts contain effective antioxidants with significant antitumor activity.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.185-196
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• 1992

To assess its suitability as a prodrug of 5-fluorouracil (5-FU), 1-glycyloxymethyl-5-FU HCl (GFU), a 5-fluorouracil derivative having a glycyloxymethyl group at the N-l position was synthetized. Its physicochemical properties and hydrolysis kinetics, in aqueous solution of pH $1{\sim}10$ and in the presence of human plasma or rat liver homogenate were studied. Its acute toxicity and antitumor activity against sarcoma 180 were also examined, GFU showed higher lipid/water partition coefficient than 5-FU. The calculated $pK_{\alpha}$ values of 5-FU and GFU were 8.02 and 7,20, respectively. The decomposition rates of GFU in aqueous solution showed a pH-dependence over the pH range used, which could be ascribed to solvent catalysed hydrolysis reaction at pH lower than 4,16 and to specific hydroxide ion hydrolysis reaction at pH higher than 4,16, The half-life of GFU was 6,9 min in 80% human plasma solution and less than 3 min in rat liver homogenate at $37^{\circ}C$, The $LD_{50}$ value of 5-FU was 240 mg/kg while that of GFU was 440.6 mg/kg (226 mg as 5-FU). Both of 5FU and GFU showed a strong antitumor activity, Therapeutic ratios of 5-FU and GFU were 3.07 and 3.55, respectively.

• Food Science and Biotechnology
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• v.16 no.4
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• pp.600-604
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• 2007

In this study, we first prepared 3 kinds of powders with different molecular masses from the crude protein-bound polysaccharide extract of Agraricus blazei Murill through ultrafiltration, followed by spray-drying. Then, the antitumor activities of the powders were analyzed. Size exclusion chromatography coupled with a multi-angle laser-light-scattering system showed the 3 powders had the following molecular ranges: below 10 kDa (SD-1), 10 to 150 kDa (SD-2), and above 150 kDa (SD-3), representing peak molecular weights of $8.26{\times}10^3,\;9.65{\times}10^4$, and $5.94{\times}10^6\;g/mol$, respectively. All the powders stimulated macrophage RAW264.7 cells to produce nitric oxide, of which SD-2 and SD-3 were superior to the crude extract powder (CP-SD), while SD-1 showed the lowest activity. Similar results were found for their cytotoxicities against human cancer cell lines (A549, MCF-7, and AGS), where the highest activity was obtained with the SD-2 treatment for 72 hr at $1,000\;{\mu}g/mL$. The MCF-7 cell line was less sensitive to the powders than the other cells. From this research we found that ultrafiltration, in combination with spray-drying, is applicable for preparing protein-bound polysaccharide powders with higher antitumor activities.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.400-408
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• 2016

Background: Ginsenoside Rh2 (GRh2) is the main bioactive component in American ginseng, a commonly used herb, and its antitumor activity had been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in HCT116 colorectal cancer cells. Methods: We examined the effect of GRh2 on HCT116 cells ex vivo. Next, we performed in vitro binding assay and in vitro kinase assay to search for the target of GRh2. Furthermore, we elucidated the underlying molecular mechanisms for the antitumor effect of GRh2 ex vivo and in vivo. Results: The results of our in vitro studies indicated that GRh2 can directly bind with PBK/TOPK and GRh2 also can directly inhibit PBK/TOPK activity. Ex vivo studies showed that GRh2 significantly induced cell death in HCT116 colorectal cancer cells. Further mechanistic study demonstrated that these compounds inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 (ERK1/2) and (H3) in HCT116 colorectal cancer cells. In vivo studies showed GRh2 inhibited the growth of xenograft tumors of HCT116 cells and inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 and histone H3. Conclusion: The results indicate that GRh2 exerts promising antitumor effect that is specific to human HCT116 colorectal cancer cells through inhibiting the activity of PBK/TOPK.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.187-192
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• 2006

Herbal medicines have been utilized to treat a variety of diseases, including cancer. Several species of the family rubiaceae have been reported to have antitumor activity. In this study, we report the cytotoxicity and antitumor activity exhibited dy the methanol extracts prepared from Rubia radix (RRME), Uncaria gambir (UGME) and Oldenlandia diffusa (ODME) (family: Rubiaceae) against human promyleloid leukemia cell line, HL-60. The cytotoxicity of RRME (2~20 ${\mu}g/ml$), UGME (20~200 ${\mu}g/ml$) and ODME (20~200 ${\mu}g/ml$) were assessed dy the MTT reduction assay. IC50 values for RRME, UGME and ODME were 11.0, 99.5 and 106.1 ${\mu}g/ml$, respectively. When the HL-60 cells were treated with RRME (10 ${\mu}g/ml$), UGME (120 ${\mu}g/ml$) and ODME (140 ${\mu}g/ml$) for 24 h, several apoptotic characteristics such as DNA fragmentation and morphologic changes were observed. Furthermore, flow cytometric analysis was peformed to determine the percent of apoptotic cells. The poupulation of sub-G1 hypodiploid cells was increased 37.49% in RRME treatment, 12.49% in UGME treatment and 7.21% in ODME treatment compared with untreated control cells (2.64%). To further confirm apoptotic cell death, we assayed caspase-3, -8 and -9 activities in RRME, UGME and ODME-treated cells. After treatment of RRME, UGME and ODME for 12 h, caspase-3, -8 and -9 activities significantly increased.compared to untreated control cells. These results show that RRME, UGME and ODME induced apoptotic cell death in HL-60 cells and may have a possibility of potential antitumor activities.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.4
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• pp.170-176
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• 2020

Palmijihwang-tang is an herbal formula frequently used to treat many symptoms, such as lumbago, pollakiuria, cold hands and feet, nephritis, sterilitas virilis, and prostatic disorders. The aim of this study was to investigate the effects of Palmijihwang-tang on cisplatin-induced nephrotoxicity in rat kidney proximal tubular NRK-52E cells. NRK-52E cells were treated with Palmijihwang-tang in absence or presence of 30 µM cisplatin for 12 or 24 h. Palmijihwang-tang at concentrations of 50-800 ㎍/ml did not change the cell viability in NRK-52E cells, and showed no significant toxicity. Palmijihwang-tang at concentrations of 400 and 800 ㎍/ml significantly increased the cell viability and reduced apoptotic cells in NRK-52E cells exposed to cisplatin. Also, Palmijihwang-tang markedly inhibited cisplatin-induced caspase-3 activation, PARP cleavage, ROS production and p53 activation in NRK-52E cells. Furthermore, Palmijihwang-tang did not interfere with the antitumor activity of cisplatin in AGS and A549 cancer cells. Particularly, Palmijihwang-tang enhanced antitumor activity of cisplatin in A549 cells. Taken together, these results suggest that Palmijihwang-tang ameliorated cisplatin-induced nephrotoxicity through reduction of ROS production and p53 activation, and did not interrupt antitumor efficacy of cisplatin against cancer cells.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.395-399
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• 1998

DW2282, (S)- (+)-4-phenyl -1-[N-(4-am mob enzoyl) -indolin-5- sulfonyl]-4,5- dihydro-2-imidazolone hydrochloride, is a novel anticancer agent thought to have an unique mechanism of action on the inhibition of tumor growth. In this study, we estimated in vivo antitumor activities and pharmacokinetics of Dw2282 depending on various vehicles. The inhibition rate of tumor growth was increased by 50, 100 and 200 mg/kg of Dw2282 in a dose-dependent manner. When Dw2282 dissolved in 4 sorts of vehicles was orally single dosed to rats at 50 mg/kg, Cmax of Dw2282 in 0.5% CMC.Na was a half as high as those in PG, PG+CP and PG+CP+DW. When Dw2282 was orally administered to mice for 5 days, antitumor activity of 130 mg/kg suspended in 0.5% CMC.Na was as effective as that of 65 mg/kg dissolved in the rest of vehicles. Taken together, it is thought that antitumor activities of Dw2282 are resulted from the absorption extent of it and related to the vehicle used.