• 생약학회지
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• 제38권2호통권149호
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• pp.117-122
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• 2007

The specific activation of the immune system to control cancer growth in vivo has been a long-standing goal in cancer immunology. Whole tumor Iysates have been used either alone or combined with adjuvants to induce specific immune response in vivo. Here, we examined whether freezing/thawing (F/T) colon26-M3.1 tumor cell admixed with EN-3, glycoprotein purified from Acanthopanx Senticosus, could stimulate in vivo immunity by using a murine experimental tumor metastasis model produced by colon26-M3.1 carcinoma cells. Vaccination of mice with F/T treated colon26-M3.1 carcinoma cells in combination with EN-3 as an adjuvant resulted in a significant inhibition in tumor metastasis of mice against live colon26-M3.1 carcinoma challenge. In addition, the splenocytes from vaccinated mice exhibited a higher proliferating activity and secreted interferon-${\gamma}$. These results suggest that EN-3 can be applied to immunoadjuvant to enhance the antitumor immunity in vivo.

• Journal of Pharmaceutical Investigation
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• 제35권5호
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• pp.361-367
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• 2005

In this study, we evaluated and compared the pharmacodynamics of paclitaxel (PTX) in human A549 NSCLC cells grown as monolayers or as three-dimensional histocultures. Growth inhibitory effects were determined after incubating cells in drug free medium until 96 hr post drug exposure initiation. Cell cycle arrest and apoptosis were measured by flow cytometry. The growth inhibition induced by PTX was significantly different in monolayers and histocultures, and PTX showed significantly less cytotoxicity in histocultures where large resistant fractions were observed. Moreover, although PIX induced significant $G_{2}/M$ arrest followed by apoptosis in monolayers in a drug concentration-dependant manner, $G_{2}/M$ arrest was not elicited in histocultures. However, apoptotic cells appeared from the $G_{2}/M$ phase in histocultures. In this study, we provide first evidence that PIX in three-dimensional histocultures, does not induce $G_{2}/M$ arrest, but rather that it induces $G_{2}/M$ phase specific apoptosis. Overall, our data demonstrate different pharmacodynamics of PTX in traditional monolayer and three-dimensional histocultures.

• Journal of Microbiology and Biotechnology
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• 제17권11호
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• pp.1856-1861
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• 2007

Physiological cell conditions such as glucose deprivation and hypoxia play roles in the development of drug resistance in solid tumors. These tumor-specific conditions cause decreased expression of DNA topoisomerase $II{\alpha}$, rendering cells resistant to topo II target drugs such as etoposide. Thus, targeting tumor-specific conditions such as a low glucose environment may be a novel strategy in the development of anticancer drugs. On this basis, we established a novel screening program for anticancer agents with preferential cytotoxic activity in cancer cells under glucose-deprived conditions. We recently isolated an active compound, AA-98, from Streptomyces sp. AA030098 that can prevent stress-induced etoposide resistance in vitro. Furthermore, LC-MS and various NMR spectroscopic methods identified AA-98 as mithramycin, which belongs to the aureolic acid group of antitumor compounds. We found that mithramycin prevents the etoposide resistance that is induced by glucose deprivation. The etoposide-chemosensitive action of mithramycin was just dependent on strict low glucose conditions, and resulted in the selective cell death of etoposide-resistant HT-29 human colon cancer cells.

• 한국자원식물학회지
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• 제33권3호
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• pp.183-193
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• 2020

Recently, as a natural substance has been emphasized interest in research to enhance the immune function. Green lettuce (Lactuca sativa L.) is a popular vegetable used fresh and it contains various phytochemicals and antioxidant compounds, and has been reported to have various physiological activities such as antibacterial, antioxidant, antitumor and anti-mutagenic. However, only a few studies have investigated on the mechanism of action of immune-enhancing activity of lettuce. Therefore, in this study, the immunomodulatory activities and potential mechanism of action of Green lettuce extracts (GLE) were evaluated in the murine macrophage cell line RAW264.7. GLE significantly increased NO levels by RAW264.7 cells, as well as expressions of immunomodulators such as iNOS, COX-2, IL-1β, IL-6, IL-12, TNF-α and MCP-1. Although GLE activated ERK1/2, p38, JNK and NF-κB, GLE-mediated expressions of immunomodulators was dependent on p38, JNK and NF-κB. In addition, TLR4 inhibition blocked GLE-mediated expressions of immunomodulators and activation of p38, JNK and NF-κB. Taken together, these results demonstrated that TLR4-MAPK/NF-κB signalling pathways participated in GLE-induced macrophage activation and GLE could be developed as a potential immunomodulating functional food.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.237-242
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• 2013

Cervical cancer is the second most common cause of cancer in women and has a high mortality rate. Cisplatin, an antitumor agent, is generally used for its treatment. However, the administration of cisplatin is associated with side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown to have anti-cancer properties. In this study, we used Noni, cisplatin, and the two in combination to study their cytotoxic and apoptosis-inducing effects in cervical cancer HeLa and SiHa cell lines. We demonstrate here, that Noni/Cisplatin by themselves and their combination were able to induce apoptosis in both these cell lines. Cisplatin showed slightly higher cell killing as compared to Noni and their combination showed additive effects. The observed apoptosis appeared to be mediated particularly through the up-regulation of p53 and pro-apoptotic Bax proteins, as well as down-regulation of the anti-apoptotic Bcl-2, Bcl-$X_L$ proteins and survivin. Augmentation in the activity of caspase-9 and -3 was also observed, suggesting the involvement of the intrinsic mitochondrial pathway of apoptosis for both Noni and Cisplatin in HeLa and SiHa cell lines.

• 약학회지
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• 제34권6호
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• pp.395-400
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• 1990

The FU-fat conjugates(4a-e) as a prodrug have been synthesized by condensing various fatty acids(1a-e) via isocyanates(2a-e) as carbamoyl group at $N^1-position$ of 5-fluorouracil and their structures characterized. Preliminary testing for their antitumor effect was carried out on leukemia L1210 cells in culture. Most of them(4a-d) like the parent FU exhibited less than 50% inhibition on grouth of the cultrued cells at the concentration of $1\;{\times\;10^{-7}M$. Only a dicarboxylic acid derivative, 4e, showed over 50% inhibition at the same level.

• International Journal of Oral Biology
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• 제39권1호
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• pp.1-7
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• 2014

Neuromedin B (NMB) acts as a growth factor or a morphogen and plays a role in cancer progression. Indeed, the NMB receptor (NMB-R) is overexpressed in different types of tumors. In our current study, we investigated the involvement of NMB-R in the proliferation of oral cancer cells. Human oral squamous cell carcinoma (SCC) and human oral cancer cells, SCC-25 cells were found to be NMB-R-positive. The NMB-R antagonist PD168368 inhibited the proliferation of SCC-25 cells and reduced their colony formation capacity. We also found that PD168368 induced the cell cycle arrest and apoptosis of SCC-25 cells in a dose-/time-dependent manner. Overall, this antitumor activity of PD168368 in human oral cancer cells suggests that NMB-R is a potential target for the future prevention and treatment of human cancers.

• 대한한의학회지
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• 제22권2호
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• pp.22-30
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• 2001

This study was attempted to investigate the anti-tumor and anti-metastatic effects of Sobokchukeotang(SBCT) and Kamisobokchukeotang(KSBCT). Cytotoxicity against various cancer cell lines, anti-adhesion, pulmonary colonization, anti-angiogenesis, and T/C% were evaluated. SBCT and KSBCT exhibited no cytotoxicity against HT-1080, A549, SK-OV-3, B16-F10 and SK-Mel-2 cell lines. In inhibitory effect on DNA topoisomerase I, the $IC_{50S}$ were shown $250-500{\;}\mu\textrm{g}/ml$ of SBCT and $62.5-125{\;}\mu\textrm{g}/ml$ of KSBCT respectively. In the in vivo experiments, SBCT(135.98%) and KSBCT(151.92%) apparently increased the life span of mice bearing sarcoma-180. KSBCT significantly inhibited the adhesion of HT-1080 to complex extracellular matrix in a dose-dependent manner in contrast to SBCT. In pulmonary colonization assay by B16-F10, a number of colonies in the lungs were decreased more significantly in KSBCT group than those in SBCT group. In vitro neovascularization and CAM assay, angiogenesis was more significantly inhibited in KSBCT-treated group than in SBCT- treated group. Above results suggests that KSBCT is more effectively applied to prevention and treatment of cancer than SBCT.

• Biomolecules & Therapeutics
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• 제3권2호
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• pp.154-158
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• 1995

We isolated Streptomyces spry. from Korean soil, which showed high cytotoxicity against tumor cell lines, L1210 and P388Dl. Among 30 strains, three strains (DKM 104, DKM 128, DKM 409) were appeared to possess plasmid. Strain DKM 104 and DKM 128 had two CCC(Covalently Closed Circular) form plasmid, about 20 Kb in size and about 1 Kb compared with λ Hind III DNA size marker. And strain DKM 409 had three plasmids, among which two plasmic were CCC form about 20 Kb and about 20 Kb compared with same size marker. To find out whether plasmid involved in production of antitumor agent or not, we performed to curing experiment. Comparing cytotoxicity between culture filtrate of plasmid-containing strains and cured strains, we knew that only the cytotoxic activity of the strain DKM 128 was involved in plasmid.

• 생약학회지
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• 제27권2호
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• pp.101-104
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• 1996

Hydrogen peroxide is one of major chemicals mediating antitumor and antimicrobial activities of macrophages. We searched natural products enhancing hydrogen peroxide generation from murine macrophage-like cell line J774. Among 21 methanol extracts of Korean medicinal plants, the extract from Cornus officinalis was the most effective. The active component from the fractions was searched by activity guided fractionation, and identified as ursolic acid by spectral data.