• Radiation Oncology Journal
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• v.23 no.1
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• pp.51-60
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• 2005

Purpose : Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods : Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy ($SF_2$) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results : A cooperative effect were observed on the apoptosis of the HeLa ceil line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of $22.70\%$ compare with combination of the one drug with radiation, apoptosis of $8.49\%$. In cell cycle analysis, accumulation of cell on $G_0/G_l$ phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity on a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and $SF_2$ of 0.12 but the combination of one drug with radiation was not enhanced radlosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion : Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.2
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• pp.272-277
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• 2010

This experimental study was performed to investigate the antitumor effect of Egg white combined-Chalcanthite (InSan 4, IS4) in xenografted nude mice with NCI-H460 human lung cancer cell. We cultured NCI-H460 cell lines and xenografted them on nude mice. These mice were divided into 3 groups; group with dose of 45 mg/kg IS4 orally, group with dose of 90 mg/kg IS4 orally, and the control group. They had been raised and treated for 28 days. We checked their body weight, tumor weight and volume twice a week, and their absolute organ weight, microhistological observation and biochemical blood analysis at the final day by sacrificing them. We also calculated their tumor inhibition rate (IR), mean survival time and percent increase in life span (% ILS). In this study, we observed that all of the IS4 treated mice have tumor regression, dosage-dependently, compared to the control group. Tumor weight and volume of high dose treated mice were smallest. IR increased in IS4 in a dose-dependent manner. Mean survival time and percent increase in life span (% ILS) in high-dose IS4 treatment group were the highest of the three groups. There was no significant difference in biochemical blood analysis, alanine phopsphatase (ALP), Calcium, creatinine (CRE), alanine transferase (ALT), and aspartate transaminase (AST) levels. The urea nitrogen (UN) level results significantly decreased by IS4 45 and 90 mg/kg (IS4 45 mg/kg, IS4 90 mg/kg, p<0.01). IS4 may have potential anti-tumor effect in a solid tumor induced by NCI-H460 without remarkable side effects.

• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.307-313
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• 1994

We have previously shown that crude water extract of Euonymus alatus (EA) had strong prophylactic effect against chemically induced-and tumor cell implanted-cancer, and that the mechanisms responsible for its antitumor effects were due to nonspecific enhancement of the NK cell activities and the cell mediated immunity. However, it was unknown that any components of crude extract did work so, since it consisted of several components. In this paper, we fractionated the crude watar EA-extract into several fraction such as hexane-, ethylether-, ethyl acetate-, n-butanol- and water soluble-fraction, and screened the immune regulating activities of each fraction by the evaluation of lymphokine production and activated lymphocyte proliferation. As a result of the component fraction of EA-extract, it was found that n-butanol fraction was a potent immunostimulator, and the remained water soluble fraction also contained some stimulator, But, other fraction did not showed any remarkable effect. It is therefore suggested that EA-glycosides in n-butanol fraction may be new one of the potent biological response modifiers. The present study was also undertaken in an efforts to investigate the effects of elm-bark(EB, Ulmus clavidiana var japonica), which has been used for curing ulcer and inflammation as a folk medicine without any kind of experimental evidence to support this, on the cellular- and humoral-immune responses, lymphocyte function and NK cell activities in mice. Regardless of time and duration of EB-treatment, Arthus reaction and antibody response to SRBC were not modified by EB, but delayed hypersensitivity to SRBC was significantly enhanced only when EB was treated prior to SRBC-sensitization. EB slightly inhibited the proliferation responses of splenocytes to PHA-stimulation, but it significantly augmented the responses of these cells to S aureus Cowan 1 and Con A-activation, and these effects were manifested only when EB was added at culture initiation. EB did not influence Ig secretion of spleen cells but it significantly augmented the Con A-induced 1L 2 and MIF production of splenocytes. NK cell activities of splenocytes were markedly riled when effector cells were pretreated with EB and this augmentation was dine to the increase of binding affinity of effector cells to target cells and the target cell lytic activities of effector cells. These results led to the conclusion that EB triggers increase of cellular immune responses, such as delayed hypersensitivitiy, lymphokine production and NK cell activities. Also these results suggested that EB contains potent immune stimulants, which may provide the rational basis for their therapeutic use as one of the new biological response modifiers.

• The Journal of Korean Medicine
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• v.17 no.1 s.31
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• pp.111-131
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• 1996

For the development of antimetastatic agent 41 kinds of crude drugs were used for the evaluation of inhibitory effect of several crude drugs on cell adhesion of pulmonary cancer cells and platelet aggregation. Results were obtained as follows: 1. Water extracts of crude drugs inhibited cell adhesion of A549 to complex extracelluar matrix over 40 % of contol were Houttuyniae Herba, Mylabris, Rhei Radix et Rhizoma, Meliae Cortex, Ferula Resina, Oldenlandiae diffusae Herba at the higher concentration of $10^{-3}g／ml$ while those inhibiting cell adhesion of Bl6-Fo over 40 % of control were $10^{-5}g／ml$ of Houttuyniae Herba, Aurantii Fructus, Lithospermi Radix, Zedoariae Rhizoma. Prunellae Spica, Foeniculi Fructus, Rbei Radix, Scutellariae Radix, Meliae Cortex, Ferula Resina and Oldenlandiae diffusae Herba. 2. MeOH extracts of crude drugs at the concentration of $4{\times}10^{-4}g／ml$ inhibiting cell adhesion of A549 specifically to single extracelluar matrix over 40 % of control were Lithospermi Radix, Agrimoniae Herba, Rhei Radix and Ferula Resina to collagen I, Houttuyniae Herba, Lithospermi Radix, Bupleuri Radix, Salviae miltiorrhizae Radix, Orostachys Herba, Sappan Lignum, Meliae cortex ferula Resina and Coicis Semen to collagen Ⅳ, Mylabris, Agrimoniae Herba to laminin, Houttuyniae Herba and Meliae Cortex to fibronectin. 3. NeOH extracts of crude drugs at the concentration of $4{\times}10^{-4}g／ml$ inhibiting cell adhesion of B16-Fo specifically to single extracelluar matrix over 60 % of control were Lithospermi Radix, Salviae miltiorrhizae Radix, Meliae Cortex and Ferula Resina to collagen I, Lithospermi Radix, Bupleun Radix, Saiviae miltiorrhizae Radix, Ferula Resina and Acanthopanacis Cortex to collagen Ⅳ, Bupleuri Radix, Orostachys Herba to laminin, Houttuyniae Herba to fibronectin. 4. MeOH extracts of crude drugs inhibiting platelet aggregation over 40% of ADP control were at the concentration of $50{\mu}g/m{\ell}$ of Houttuyniae Herba, Angilicae gigantis Radix, Zedoariae Rhizoma. Coicis Semen and $100{\mu}g/m{\ell}$ of Ferula Resina, Orostachys Herba, Salviae miltiorrhizae Radix, Curcumac Radix, Carthami Flos, Lithospermi Radix, Gleditsiae Spina, Sappan Lignum, Acanthopanacis Cortex. These results suggest that several crude drugs including Ferula Resina, Houttuyniae Herba, Lithospermi Radix and Salviae miltiorrhizae Radix chiefly have more possibility to exert antimetastatic activity and require in vivo antimetastatic study.

• The Korean Journal of Mycology
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• v.34 no.2
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• pp.98-104
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• 2006

Armillaria mellea, one of edible and medicinal mushroom belonging to Tricholomataceae of Basid-iomycota, has been known to have outstanding inhibitive effects on the sarcoma 180 and Erhrlich carcinoma of mice. Neutral salt soluble (0.9% NaCl), hot water soluble and methanol soluble substances (hereinafter referred to Fr. NaCl, Fr, HW and Fr. MeOH, respectively) were extracted from the mushroom. In vitro cytotoxicity tests, crude polysaccharide were not cytotoxic against cancer cell lines such as NIH3T3 and Sarcoma 180 at the concentration of $1000{\mu}g/ml$. Intraperitoneal injection with crude polysaccharides exhibited life prolongation effect of $60{\sim}67.5%$ in mice inoculated with Sarcoma 180, respectively. Fr, NaCl improved the immunopotentiation activity of B lymphocyte by increasing the alkaline phosphatase activity by $1.8{\sim}3.0$ folds, respectively. In case of Fr. NaCl, the numbers of peritoneal exudate cells and circulating leukocytes were increased by 10 and 2 folds, respectively.

• Journal of Life Science
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• v.17 no.6 s.86
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• pp.748-755
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• 2007

The in vitro activity of ST1571, an inhibitor of the Abl group of protein-tyrosine kinases, alone or in combination with camptothecin (CPT), a specific topoisomerase I inhibitor, was evaluated against human cancer cells with different metastatic capacity and drug resistance potency. These cell lines showed different sensitivity to ST157 on growth inhibition, and the expression of DNA-dependent protein kinase (DNA-PK), which interacts constitutively with c-Abl, was significantly decreased in drug sensitive CEM and MCF-7 cells and poorly metastatic PC3 and KMl2 cells as compared with that of multidrug resistant CEM/MDR and MCF-7/MDR cells and highly metastatic PC3-MM2 and KM/L4a cells, respectively. These results suggest differential modulation of DNA-PK by ST1571 treatment in drug resistance and metastatic degree dependent manner. We showed that CPT as well as ST1571 significantly inhibits the expression of DNA-PK. The combined treatment with ST15fl and CPT revealed synergistic effect, and the effect was accompanied by inhibition of cell proliferation due to significant reduced expression of DNA-PK components, which resulted in CPT sensitizes human cancer cells resistant to ST1571. Therefore, the results of our study suggested that the suppression of DNA-PK using combination of ST1571 and CPT could be a novel molecular target for against drugresistant and metastatic cancer cells.

• Journal of Life Science
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• v.33 no.5
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• pp.414-421
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• 2023

Cnidium japonicum (C. japonicum) is a type of halophyte that inhabits soil of a high salinity, and according to previous studies, it is known to have antitumor effects. However, the skin's protective effect, particularly against UVB irradiation, has not been revealed. In this study, C. japonicum crude extract was studied to determine its effect on damage to human keratinocytes (HaCaT) induced by UVB irradiation, and ROS assays were performed, the results of which showed that C. japonicum crude extract affects UVB-induced photoaging damage in human keratinocytes. To examine inhibitory effects against the expressions of MMPs, RT-PCR and Western blot assay were performed by treating the crude extract at concentrations of 10, 50, and 100 ㎍/ml by irradiating UVB at 15 mJ/cm². As a result, it was confirmed that the mRNA and protein expression levels of MMP-1, MMP-3, and MMP-9 decreased in the group treated with C. japonicum crude extract, which also effectively regulated the antioxidant defense mechanism pathway by activating JNK, ERK, and p38. In conclusion, the current study suggested the possibility that C. japonicum could be used as a raw material for anti-photoaging cosmeceuticals in the future.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.87-96
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• 1994

Background : Since tumor necrosis factor was discovered in 1975, TNF has been well known about its cytotoxic effect on tumor cells in vivo and in vitro. According to the recent improvement of molecular biological techinques, it is possible that exogenous TNF gene is transferred to tumor cells and is expressed in theirs. By virtue of TNF gene transfer, we have expected that TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells in vivo without systemic side effect. The expected mechanisms in which antitumor effects of TNF expressed in TNF-gene-transferred tumor cells are working would be as followings. In the first mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells around(like homicide). In the second mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill themselves(like suicide). In the third mechanism, TNF expressed in TNF-gene-transferred tumor cells would recruit immune effector cells and kill tumor cells indirectly. In the last mechanism, TNF expressed in TNF-gene-transferred tumor cells would augment cytokine such as interferon-$\gamma$ to kill tumor cells. Among these four mechanisms of antitumor effect, only the second mechanism has not been established yet. Therefore, to elucidate the second mechanism, We performed this study. Method : We transferred TNF-$\alpha$ gene to NCI-H2058, a human mesothelioma cell line and WEHI164, a murine fibrosarcoma cell line by using retroviral vector(pLT12SNTNF). And, We determined by using MTT assay whether TNF expressed in TNF-gene-transferred tumor cell lines would kill themselves like suicide or not. Then, if TNF-gene-transferred tumor cell lines would not suicide themselves, I would know more about the TNF sensitivity of TNF-gene-transferred tumor cell lines to exogenous TNF also by MTT assay. Result : NCI-H2058 and WEHI164 which were sensitive to TNF, became far less sensitive to endogenous and exogenous TNF after being transferred TNF-$\alpha$ gene to. Conclusion : TNF-gene-transfer to NCI-H2058 and WEHI164 gave them resistance to TNF.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.2
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• pp.69-78
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• 2017

Cordyceps militaris has been used in traditional Chinese medicine owing to its anticancer and immunomodulatory activities. Germanium compounds have also been shown to be associated with many pharmacological functions, such as antimicrobial, antiviral, antitumor, antimutagenic, and immunomodulating effects. In this study, we examined the biological properties of hot water extract from mycelial liquid culture of germanium-enriched C. militaris (CMGe). CMGe displayed a concentration-dependent antiproliferation activity against four human cancer cell lines. The antiproliferative activity of CMGe was 2-4-fold lower than that of hot water extract from mycelial liquid culture in C. militaris (CM). However, CM had a concentration-dependent cytotoxicity to human bone marrow-derived mesenchymal stem cells (MSCs). Contrastingly, CMGe did not cause any cellular damage to MSCs. MSCs cultured with CMGe displayed an increased proliferative activity with no cytotoxic effect. The oral administration of CMGe inhibited increased tumor volume and weight compared with the control group. CMGe has the potential to be used as an industrial product in medicinal foods as well as in pharmaceutical products.

• Journal of Acupuncture Research
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• v.19 no.4
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• pp.56-73
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• 2002

Objective : We need to develop a new treatment method which can curve cancer growth and enhance immunity of patients with various kinds of cancer more safely and effectively, for conventional anticancer treatment has lots of problems to be overcomed, in other words, Its efficacy can be recognizible but it doesn't actually give aid to patients due to its side effects. This study was taken up to evaluate the anticancer and immune-enhancing effect of Scutellariae Barbatae Herba, Alli bulbus, Oldenlandiae Herba(SAO) Herbal acupuncture. Methods : SAO Herbal acupuncture solution was made from Scutellariae Barbatae Herba, Alli bulbus, Oldenlandiae Herba by decoction. Experimental group was divided into normal(N), control(TC, cancer group induced by S 180), high and low concentration SAO complex Herbal acupuncture group. In the high and low concentration SAO complex Herbal acupuncture group, SAO Herbal acupuncture solution was injected, on the left and right Chok-samni(足三里, ST36) of ICR-male S 180 rats alternatively, by 200mg/kg and 100mg/kg respectively. In vitro, S 180 was cultured with $200{\mu}g$ and $500{\mu}g$ of SAO Herbal acupuncture solution. In each experimental group, we examined the effect of SAO complex Herbal acupuncture on body weight, antitumor, organ weight, activity of macrophage, activity of B cell, spleen cell division, IL-2 production and population of lymphocytes. Results : 1. In Body weight, no significant change was shown, but In solid cancer weight, the high concentration SAO complex Herbal acupuncture group showed signigicant(P<0.05) decrease and significant(P<0.05) increase in the weight of kidney, compared with control group. 2. In activity of macrophage, low concentration SAO complex Herbal acupuncture group showed significant(P<0.01) increase, but in vitro, there was no significant increase, compared with control group. 3. In activity of B cell, high and low concentration SAO complex Herbal acupuncture group showed no significant decrease, but in vitro, low concentration SAO complex Herbal acupuncture group showed significant(P<0.01) increase, compared with control group. 4. In spleen cell division, high and low concentration SAO complex Herbal acupuncture group had no significant influence on spleen cell division induced by Co A, meanwhile, it was found that macrophge promote spleen cell division in low concentration SAO complex Herbal acupuncture group(P<0.05), compared with control group. 5. In IL-2 production, high concentration SAO complex Herbal acupuncture group showed significant((P<0.05) increase, compared with control group. 6. In population of lymphocytes, high concentration SAO complex Herbal acupuncture group showed significant increase of CD3+(P<0.05), CD4+(P<0.05), CD3+ and CD4+ T cell(P<0.01) and B cell(P<0.05), while low concentration SAO complex Herbal acupuncture group showed significant increase of CD4+(P<0.05), CD8+ T cell(P<0.05) and B cell(P<0.01), compared with control group. Conclusion : SAO Herbal acupuncture inhibited cancer growth and enhanced immunity.