• 생명과학회지
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• 제9권6호
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• pp.677-683
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• 1999

Gamdutang aqua-acupuncture solution (GAS), Gamdutang water-extracted solution (GWS) and Dae-Gamdutang aqua-acupuncture solution (DGAS) were prepared and tested for antitumor activities. It was shown to possess considerable toxicity toward various tumor cell lines. Concentration of 5 $\times$ and 10$\times$ of GAS resulted in more than 70% inhibition of growth in Ehrlich ascites tumor cells (EATC), Hepa1c1c7 and A549. GAS at concentrations of 5$\times$ and 10$\times$ revealed more than 60% inhibition in HeLa. GWS showed more than 50% inhibition of growth with EATC and HeLa at concentrations of 5$\times$ and 10$\times$, respectively. Toxicity assay with GWS in Hepa1c1c7 and A549 revealed that more than 80% inhibition of growth at the concentration of 5$\times$ and 10$\times$. In morphological study, the number of cells were decreased, and the shape of cells was round-form in EATC, Hepa1c1c7, A549, HeLa with GAS.

• BMB Reports
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• 제32권2호
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• pp.173-180
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• 1999

The effects of agmatine on the enzymes responsible for the biosynthesis of polyamines, the resultant levels of polyamines, and their effect on the growth of DU145 human prostate tumor cells were investigated. When agmatine was added to the medium, ornithine decarboxylase (ODC, EC 4.1.1.17) activity was substantially reduced, but S-adenosylmethionine decarboxylase (SAMDC, EC 4.1.1.50) activity increased markedly. These changes in ODC and SAMDC activities were the result of an induction of ODC-antizyme and a decreased turnover rate of SAMDC in the presence of agmatine. Accordingly, there was a decrease in the intracellular levels of putrescine and spermidine but an increase in the intracellular level of spermine. Cell growth was markedly inhibited by agmatine treatment and this inhibition was not recovered by the addition of putrescine or spermidine. Our results suggest that agmatine alters the intracellular amounts of polyamine in the cells, closely related to the inhibition of cell growth.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권1호
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• pp.59-70
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• 2008

Purpose: We evaluated the therapeutic effect of AEE788, a dual inhibitor of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinases on human salivary adenoid cystic carcinoma (ACC) cells growing in nude mice. Experimental Design: We examined the effects of AEE788 on salivary ACC cell growth and apoptosis. To determine the in vivo effects of AEE788, nude mice with orthotopic parotid tumors were randomized to receive oral AEE788 (50 mg/kg) three times per week, injected paclitaxel ($200{\mu}g$) once per week, AEE788 plus paclitaxel, or placebo. Mechanisms of in vivo AEE788 activity were determined by immunohistochemical analysis. Results: Treatment of salivary ACC cells with AEE788 led to growth inhibition and induction of apoptosis. AEE788 inhibited tumor growth and prevented lung metastasis in nude mice. Furthermore, AEE788 potentiated growth inhibition and apoptosis of ACC tumor cells mediated by paclitaxel. Tumors of mice treated with AEE788 and AEE788 plus paclitaxel exhibited down-regulation of activated EGFR and its downstream mediators (Akt and MAPK), increased tumor and endothelial cell apoptosis, and decreased microvessel den-sity, which correlated with a decrease in the level of MMP-9, MMP-2 and bFGF expression and a decrease in the incidence of vascular metastasis. Conclusions: These data show that tumor-associated endothelial cells are important in the process of tumor-metastasis. And VEGFR can be a molecular target for therapy of metastatic lung lesion of salivary ACC.

• Journal of Ginseng Research
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• 제14권2호
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• pp.244-252
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• 1990

Antitumor polyacetylenic alcohol, panaxytriol (Cl7 H26O3), was isolated and purified from a powder of the root of Pnnnx tin.1.encl C.A. Meyer. Panaxytriol possesses unusual property of being soluble in both water and organic solvents. Panaxytriol inhibited the growth of various kinds of human cultured cell lines in dose-dependent fashion in vitro. The in vivo effects of panaxytriol were tested against C57BL/6 mice transplanted with Bl6 melanomas. Panaxytriol (8 and 40 mg/kg) administered intra-muscularly(im) produced significant tumor growth delays in mice. Although a detailed mechanism of growth inhibition by panaxytriol is unknown, preliminary results appear to implicates a surface membrane site of action. And its action seems to be more dose-dependent than time-dependent. Finally, panaxytriol pharmacokinetics was evaluated in mice given single 8 mg/kg doses intraperitoneally (ip) or im. Serum panaxytriol content was measured using both tumor growth inhibitory assay and a gas chromatographic method. The maximum serum panaxytriol content after ip and im administration was 35.0 and 1.6 $\mu$g/ml respectively. These results indicate that the compound may act as cytotoxic substance even in patients.

• 한국식품과학회지
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• 제36권1호
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• pp.141-146
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• 2004

여러 발표에서 버섯추출물의 간접적 항종양효과에 대해 보고 되고 있다. 본 연구는 표고버섯의 직접적인 종양세포주 성장억제효과를 탐지하기 위하여 휴먼자궁경부암바이러스 타입 16의 종양유전자가 발현된 동물종양세포주(TC-1)를 이용하였다. 여러 추출용매 중 물을 이용한 추출액에서 TC-1 세포주의 성장억제효과를 탐지할 수 있었다. 이들 세포성장저해는 추출물첨가농도에 상응하며 $IC_{50}$는 $800\;{\mu}g/mL$로 계산되었다. 또한, 표고버섯 물 추출물은 휴먼자궁경부암세포주(CaSki and HeLa)에서도 유사한 세포성장억제효과를 보여 주었다. 첨가농도가 1.5 mg/mL에서는 첨가후 6시간째에 벌써 완전한 종양세포주(TC-1)의 성장억제가 탐지되었다. 이들 추출물을 열처리시 종양세포주성장억제가 소실되었으나 pH의 변화에서는 그대로 종양세포주성장억제효과가 탐지되었다. 이는 표고버섯 물 추출물 내에 있는 항종양물질이 열에 민감함을 의미한다. Annexin V 및 propidium iodide 염색에 의해 이들 TC-1종양세포주의 성장 억제효과는 apoptosis에 의해 매개됨을 보여 주었다 동물실험에서 표고버섯 물 추출물의 구강투여시 TC-1유래 종양의 성장 및 생성에 아무 효과를 주지 못하였다. 반면, 형성된 종양에 직접 주사시 종양크기의 감소가 탐지되었다. 요약하면 이들 연구에서 표고버섯 물 추출물에 존재하는 항암물질은 열에 민감하며 apoptosis에 의해 휴먼자궁경부암종양유전자에 의해 종양화된 세포주의 세포성장을 직접 억제하는 기능이 있음을 증명한다.

• Journal of Microbiology and Biotechnology
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• 제10권3호
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• pp.399-404
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• 2000

The adjuvant effect of a muramyl dipeptide (MDP) derivative, MDP-Lys(L18), on enhancing of antitumor immunity induced by X-irradiated tumor cells against highly metastatic B16-BL6 melanoma cells was examined in mice. Mice immunized intradermally (i.d.) with a mixture of X-irradiated B16-BL6 cells and MDP-Lys (L18) [Vac+MDP-Lys (L18)] followed by an intravenous (i.v.)inoculation of $10^4$ viable tumor cells 7 days after immunization, showed a significant inhibition of experimental lung metastasis of B16-BL6 melanoma cells. The most effective immunization for the prophylactic inhibition of tumor metastasis was obtained from the mixture of $100{\;}\mu\textrm{g}$ of MDP-Lys (L18) and $10^4$ X-irradiatied tumor vaccine. Furthermore, immunization of mice with Vac+MDP-Lys(L18), 3 days after tumor challenge, resulted in a significant inhibition of lung metastasis of B16-BL6 melanoma cells in an experimental lung metastasis model. Similarly, the administration of Vac+MDP-Lys(L18), 1 or 7 days after tumor removal, markedly inhibited tumor metastasis of B16-BL6 in a spontaneous lung metastasis model. When Vac+MDP-Lys (L18) was i.d. administered 3 days after subcutaneous (s.c.) inoculation of tumor cells ($5{\times}10^5/site$) on the back, mice treated with Vac+MDP-Lys(L18) showed inhibition of significantly tumor growth on day 20. These results suggest that MDP-Lys (L18) is able to enhance antitumor activity induced by X-irradiated tumor vaccine to reduce lung metastasis of tumor cells, and is a potent immunomodulating agent which may be applied prophylactically as well as therapeutically to treatment of cancer metastasis.

• Advances in Traditional Medicine
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• 제7권5호
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• pp.459-465
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• 2008

The present study was undertaken to investigate the effect of in vivo administration of neem oil intra-peritoneally (i.p.) to mice bearing a progressively growing transplantable T cell lymphoma of spontaneous origin, designated as Daltons lymphoma (DL), on the tumor growth. Mice were administered various doses of neem oil mixed in groundnut oil, which was used as a diluting vehicle or for administration to control DL-bearing mice. Administration of neem oil resulted in an acceleration of tumor growth along with a reduction in the survival time of the tumor-bearing host. Neem oil administered DL-bearing mice showed an augmented apoptosis in splenocytes, bone marrow cells and thymocytes along with an inhibition in the anti-tumor functions of tumor-associated macrophages. Thus this study gives an altogether a novel information that neem oil instead of the popular belief of being anti-tumor and immunoaugmentary may in some tumor-bearing conditions, behave in an opposite way leading to an accelarated tumor progression along with a collapse of the host's anti-tumor machinery. These observations will thus have long lasting clinical significance, suggesting caution in use of neem oil for treatment of cancer.

• Nutrition Research and Practice
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• 제4권3호
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• pp.177-182
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• 2010

The Chaga mushroom (Inonotus obliquus) has been used in folk medicine to treat cancers. However, limited information exists on the underlying anticancer effects of the major component of I. obliquus in vivo. We hypothesize that the pure compounds ($3{\beta}$-hydroxy-lanosta-8,24-dien-21-al, inotodiol and lanosterol, respectively) separated from I. obliquus would inhibit tumor growth in Balbc/c mice bearing Sarcoma-180 cells (S-180) in vivo and growth of human carcinoma cells in vitro. To test this hypothesis, the growth inhibition of each subfraction isolated from I. obliquus on human carcinoma cell lines (lung carcinoma A-549 cells, stomach adenocarcinoma AGS cells, breast adenocarcinoma MCF-7 cells, and cervical adenocarcinoma HeLa cells) was tested in vitro. Then, after S-180 implantation, the mice were fed a normal chow supplemented with 0, 0.1 or 0.2 mg of subfraction 1, 2 or 3 per mouse per day. All of the subfractions isolated from I. obliquus showed significant cytotoxic activity against the selected cancer cell lines in vitro. Subfraction 1 was more active than subfraction 2 and subfraction 3 against the A549, AGS and MCF-7 cancer cell lines in vitro. In in vivo results, subfraction 1 isolated from I. obliquus at concentrations of 0.1 and 0.2 mg/mouse per day significantly decreased tumor volume by 23.96% and 33.71%, respectively, as compared with the control. Subfractions 2 and 3 also significantly inhibited tumor growth in mice bearing S-180 as compared with the control mouse tumor. Subfraction 1 isolated from I. obliquus showed greater inhibition of tumor growth than subfractions 2 and 3, which agrees well with the in vitro results. The results suggest that I. obliquus and its compounds in these subfractions isolated from I. obliquus could be used as natural anticancer ingredients in the food and/or pharmaceutical industry.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.309-314
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• 2013

Aim: Brain tumors almost universally have fatal outcomes; new therapeutics are desperately needed and will only come from improved understandins of glioma biology. Methods: Exosomes are endosomally derived 30~100 nm membranous vesicles released from many cell types. Examples from GL26 cells were here purified using density gradient ultracentrifugation and monitored for effects on GL26 tumor growth in C57BL/6j mice (H-2b). Lactate dehydrogenase release assays were used to detect the cytotoxic activity of CD8+T and NK cells. Percentages of immune cells producing intracellular cytokines were analyzed by FACS. Results: In this study, exosomes from murine-derived GL26 cells significantly promoted in vivo tumor growth in GL26-bearing B6 mice. Then we further analyzed the effects of the GL26 cells-derived exosomes on immune cells including CD8+T, CD4+T and NK cells. Inhibition of CD8+T cell cytotoxic activity was demonstrated by CD8+T cell depletion assays in vivo and LDH release assays in vitro. The treatment of mice with exosomes also led to a reduction in the percentages of CD8+T cells in splenocytes as determined by FACS analysis. Key features of CD8+T cell activity were inhibited, including release of IFN-gamma and granzyme B. There were no effects of exosomes on CD4+T cells and NK cells. Conclusion: Based on our data, for the first time we demonstrated that exosomes from murine derived GL26 cells promote the tumor growth by inhibition of CD8+T cells in vivo and thus may be a potential therapeutic target.

• 약학회지
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• 제38권5호
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• pp.579-585
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• 1994

Antitumor activity was tested by administration of reaction mixture of green onion extract and chitin to mice bearing sarcoma-180 cells. An intraperitoneal injection of mixture(20 mg/kg/day) to mice Have an 52% inhibition of tumor growth. Inhibition of tumor growth was found to be dose-dependent. When eighty miligrams of the mixture were administered, the weight of tumor was reduced significantly. HPLC analysis indicated the mixture was composed of N-acetyl-D-glucosamine, N-acetylchitobiose and N-acetylchitotriose.