• Journal of the Korean Society of Food Science and Nutrition
• /
• v.44 no.11
• /
• pp.1629-1636
• /
• 2015

The edible mushroom Agaricus blazei Murill is known to have many physiological functions, including antitumor, antiviral, and anti-inflammatory effects. Aqueous extracts were obtained by extracting A. blazei in water at $90^{\circ}C$ for 15 h, followed by spray-drying with dextran at a 70:30 ratio. In this study, we examined the immunomodulatory effect of A. blazei Murill water extract (ABM) in BALB/c mice. Mice were administered orally with 4, 20, and 100 mg/kg of ABM for 21 days. ABM-treated mice did not show significant differences in body and organ weights compare to saline-treated control mice. Splenocytes isolated from ABM-administered mice revealed similar levels of cellularity and proliferation compared to control mice, whereas they showed increased natural killer (NK) cell activity and decreased IL-4 and IL-12 production. Different from in vivo results, splenocytes isolated from normal mice showed increased proliferation and $INF-{\gamma}$ production following ABM treatment in vitro. In addition, ABM treatment enhanced macrophage proliferation and nitric oxide (NO) production in a dose-dependent manner. However, ABM had no effect on LPS-induced NO production. These results suggest that A. blazei modulates immune function by increasing NK cell activity and macrophage function.

• Journal of Ginseng Research
• /
• v.41 no.3
• /
• pp.330-338
• /
• 2017

Background: Ginsenoside Rh2 (G-Rh2) is a ginseng saponin that is widely investigated because of its remarkable antitumor activity. However, the molecular mechanism by which (20S) G-Rh2 triggers its functions and how target animals avoid its cytotoxic action remains largely unknown. Methods: Phage display was used to screen the human targets of (20S) G-Rh2. Fluorescence spectroscopy and UV-visible absorption spectroscopy were used to confirm the interaction of candidate target proteins and (20S) G-Rh2. Molecular docking was utilized to calculate the estimated free energy of binding and to structurally visualize their interactions. MTT assay and immunoblotting were used to assess whether human serum albumin (HSA), bovine serum albumin (BSA), and bovine serum can reduce the cytotoxic activity of (20S) G-Rh2 in HepG2 cells. Results: In phage display, (20S) G-Rh2-beads and (20R) G-Rh2-beads were combined with numerous kinds of phages, and a total of 111 different human complementary DNAs (cDNA) were identified, including HSA which had the highest rate. The binding constant and number of binding site in the interaction between (20S)-Rh2 and HSA were $3.5{\times}10^5M^{-1}$ and 1, and those in the interaction between (20S) G-Rh2 and BSA were $1.4{\times}10^5M^{-1}$ and 1. The quenching mechanism is static quenching. HSA, BSA and bovine serum significantly reduced the proapoptotic effect of (20S) G-Rh2. Conclusion: HSA and BSA interact with (20S) G-Rh2. Serum inhibited the activity of (20S) G-Rh2 mainly due to the interaction between (20S) G-Rh2 and serum albumin (SA). This study proposes that HSA may enhance (20S) G-Rh2 water solubility, and thus might be used as nanoparticles in the (20S) G-Rh2 delivery process.

• Journal of Society of Preventive Korean Medicine
• /
• v.13 no.2
• /
• pp.51-64
• /
• 2009

Objective : This research was aimed to investigate the anti-tumor effect, safety, mechanism and metabolizing enzyme of Agrimonia pilosa LEDEB(APL) in female C57B/L mouse. Methods : At first, to evaluate the anti-tumor activity of APL, we divided into four groups, normal, control, APL100(100mg/kg), APL150(150mg/kg). LLC obtained American Type Culture Collection was used. LLC had been inoculated to induce tumor. To measure the anti-tumor effect of APL, we calibrate tumor size and weight. To study for mechanism of anti-tumor in APL, we used western blotting and to know metabolizing enzyme in APL we used to real-time PCR. Results : APL100, APL150 inhibited tumor growth after medicine injected. APL did not only induced caspase-dependent apoptosis in LLC-bearing mouse tumor. In APL100, it were decreased 72% in CYP3A11. In APL150, it were decreased 62%, 75% in CYP3A11 and MRP1a respectively. Conclusion : These results suggests that APL has some anti-tumor effects in female C57B/L mouse tumor. APL should be careful use with other drugs related with CYP3A11 or MRP1a.

• Journal of Oriental Physiology
• /
• v.14 no.2 s.20
• /
• pp.229-237
• /
• 1999

Hwanhonsan has been used for curing tumor as a Oriental medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Hwanhonsan extract against cancer, and to study some mechanisms responsible for its effect. Some kind of tumors were induced by the typical application of 3-methylcholanthrene(MCA) or by the implantation of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(S180 cells) and FasII cells. Treatment of the Hwanhonsan extract(daily 1 mg/mouse, i.p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 hrs. Against squamous cell carcinoma induced by MCA, Hwanhonsan decreased. not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Hwanhonsan also significantly suppressed the development of 3LL cells and S180 cells implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Hwanhonsan extract into TBM. However, when tumor was induced by FsaII cells implantation, the growth of implanted cells in mice was delayed by the water extract of Hwanhonsan until 7 days and then rapid growth ensued. In vitro treatment of Hwanhonsan extract had no inhibitory effect on the tumor induced by some kind of cell lines such as A431 cells strain but it significantly inhibited the proliferation of 3LL cells, S180 cells. These results suggested that Hwanhonsan extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells.

• Journal of Ginseng Research
• /
• v.39 no.1
• /
• pp.22-28
• /
• 2015

Background: Sun ginseng (SG), a specific formulation of quality-controlled red ginseng, contains approximately equal amounts of three major ginsenosides (RK1, Rg3, and Rg5), which reportedly has antitumor-promoting activities in animal models. Methods: MTT assay was used to assess whether SG can potentiate the anticancer activity of epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells; apoptosis status was analyzed by annexin V-FITC and PI and analyzed by flow cytometry; and apoptosis pathway was studied by analysis of caspase-3, -8, and -9 activation, mitochondrial accumulation of Bax and Bak, and cytochrome c release. Results: SG remarkably enhances cancer cell death induced by epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells. Results of the mechanism study highlighted the cooperation between SG and epirubicin or paclitaxel in activating caspase-3 and -9 but not caspase-8. Moreover, SG significantly increased the mitochondrial accumulation of both Bax and Bak triggered by epirubicin or paclitaxel as well as the subsequent release of cytochrome c in the targeted cells. Conclusion: SG significantly potentiated the anticancer activities of epirubicin and paclitaxel in a synergistic manner. These effects were associated with the increased mitochondrial accumulation of both Bax and Bak that led to an enhanced cytochrome c release, caspase-9/-3 activation, and apoptosis. Treating cancer cells by combining epirubicin and paclitaxel with SG may prove to be a novel strategy for enhancing the efficacy of the two drug types.

• Biomolecules & Therapeutics
• /
• v.30 no.3
• /
• pp.274-283
• /
• 2022

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer. However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.3
• /
• pp.587-595
• /
• 1998

Background: Recombinant adenovirus hold promise as vectors to carry therapeutic genes for several reasons: 1) they can infect both dividing and non-dividing cells; 2) they have the ability to directly transduce tissues in vivo; 3) they can easily be produced in high titer; and 4) they have an established record of safety as vaccination material. However, one of the major limitation in the use of adenoviruses is that transgene expression is quite short because adenovirusees insert their DNA genome episomally rather than by chromosomal integration, and an immune response against the virus destroys cells expressing the therapeutic gene. Since sodium butyrate has been reported to induce adenovirus-mediated gene expression, we hypothesized that treatment of tumor cells, transduced with herpes simples virus thymidine kinase(HSVtk) gene using adenoviral vector, with butyrate could augment the effect of gene therapy. Methods: We transduced HSVtk gene, driven by the cytomegalovirus promoter, into REN cell line(human mesothelioma cell line). Before proceeding with the comparison of HSVtk/ganciclovir mediated bystander killing, we evaluated the effect of butyrate on the growth of tumor cells in order to rule out a potential antitumor effect of butyrate alone, and also on expression of HSVtk gene by Western blot analysis. Then we determined the effects of butyrate on bystander-mediated cell killing in vitro. Results: There was no inhibition of growth of cells exposed to butyrate for 24 hours at a concentration of 1.5mM/L. Toxic effects were seen when the concentration of butyrate was greater than 2.0mM/L. Gene expression was more stable and bystander effect was augmented by butyrate treatment of a concentration of 1.5mM/L. Conclusion: These results provide evidence that butyrate can augment the efficiency of cell killing with HSVtk/GCV system by inducing transgene expression and may thus by a promising new approach to improve responses in gene therapy using adenoviral vectors.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
• /
• v.4 no.1
• /
• pp.37-53
• /
• 1998

The sprig of Jinryungtang Gagambang has been used for curing as a traditional medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Jinryungtang Gagambang extract against cancer, and to study some mechanisms responsible for its effect. The cytotoxic and antitumor effects were evaluated on human cell liens (A549, hep3B, Caki-1, Sarcoma 180) after exposure to Jinryungtang Gagambang extract using in ILS, colony forming efficency and SRB assay which were regarded as a valuable method for cytotoxic and antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows. 1. As a result of exposure to Jinryungtang Gagambang extract, the proliferation of A549, hep3B, Caki-1, good correlations were shown from the results of SRB assay and those of clogenetic assay. 2. The oral administration of Jinryungtang Gagambang extract showed significant effects of increase of MST(mean survival time) and ILS(increased life span) depending on the increasing concentration. 3. Against squamous cell carcinoma induced by MCA, Jinryungtang Gagambang decreased not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Jinryungtang Gagambang also significantly suppressed the development of 3LL cell-implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Jinryungtang Gagambang extract into TBM. 4. Jinryungtang Gagambang extract also increased NK cell activities. According to the above results, it could be suggested that Jinryungtang Gagambang extract has prominent antiutmor effect.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.44 no.4
• /
• pp.516-523
• /
• 2015

This study investigated the antimutagenic and anticancer effects of Platycodon grandiflorum extract (PGE) and its fractions against carcinogenic N-nitrosodimethylamine (NDMA) and genotoxicity. The Ames Salmonella mutagenicity test employing histidine mutants of Salmonella Typhimurium TA98 and TA100 was used to examine the mutagenicity of PGE and its fractions. Bacterial reversion assay with S. Typhimurium TA98 and TA100 did not show a significantly increased number of revertant colonies. The same test was used to examine the ability of PGE and its fractions to prevent acquisition of N-methyl-N'-nitro-N-nitrosoguanidine- and 4-introquino-line-1-oxide-induced mutations. PGE and its fractions inhibited mutagenesis in a dose-dependent manner. Among the fractions, ethyl acetate fraction from PGE (PGEA) exhibited a higher antimutagenic effect than other fractions. PGE and its fractions suppressed the growth of cancer cell lines, including human cervical adenocarcinoma, human hepatocellular carcinoma, human breast adenocarcinoma, human lung carcinoma, and transformed primary human embryonic kidney cells. In addition, we evaluated the antitumor activity of PGEA and its fractions in sacorma-180 solid tumor-bearing mice. In vivo anticancer activity results showed that PGE and its fractions could more effectively suppress tumor growth than the control. PGEA showed higher in vitro and in vivo anticancer effects than PGE and other fractions, and PGEA inhibited NDMA formation. Thus, we showed that PGEA has antimutagenic and anticancer activities, making it a candidate anticancer material under these experimental conditions.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.25 no.3
• /
• pp.40-60
• /
• 2012

Objectives: The object of this study was to observe antitumor, anticachexia and immunomodulatory effects of Shipyeukmiyeugi-eum(SYM) on human breast cancer cell, MCF-7, xenograft Balb/c nu-nu nude mice. Methods: Three different dosages of SYM-125, 250 and 500 mg/kg were orally administered once a day for 28 days from 11 days after tumor cell inoculation, and the changes on the body weights, tumor volume and weights, weights of spleen and popliteal lymph node and epididymal fat, serum IL-6 and IFN-${\gamma}$ levels, NK cell and peritoneal macrophage activities, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents were observed. In addition, histopathological observations of apoptotic cell, spleen, popliteal lymph node and cervical brown adipose were also detected. The results were compared with a potent cytotoxic estrogen receptor antagonist, Tamoxifen 20 mg/kg treated mice. Results: Tumor volumes and weights were decreased without cytotoxic effects on the both MCF-7 and MCF-10A cells as results of all three different dosages of SYM treatment. And weights of body, spleen, popliteal lymph node, epididymal fat, serum IFN-${\gamma}$, NK cell, peritoneal macrophage activities, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents were increased with decrease of serum IL-6. At histopathological observations, apoptotic tumor cells, spleen, popliteal lymph node and cervical brown adipose tissue were increased. That means tumor-related immunosuppress and cachexia were markedly inhibited by SYM treatment as compared with tumor-bearing mice. On the other hand, Tamoxifen showed marked cytotoxic effects against MCF-7 and MCF-10A, decreases of tumor volume and weights, and increases of apoptotic tumor cells and related decreases of tumor cell volumes, but tamoxifen markedly deteriorated the tumor-related immune-suppress and cachexia. Conclusions: The results obtained in this study suggest that SYM showed favorable anticancer effects and anticachexic effects on the MCF-7 cell xenograft through immunomodulatory effects. SYM did not induce any cytotoxic effects against both normal and cancer cells.