• The Journal of Korean Obstetrics and Gynecology
• /
• v.22 no.1
• /
• pp.31-40
• /
• 2009

Purpose: This study was carried out to investigate the anti-tumor metastasis effect and activation of innate immunity by extracts of Mori radicis cortex. Methods: Anti-tumor metastatic experiment was conducted in vitro and in vivo by using colon 26-M3.1 carcinoma cell, L5178Y-R lymphoma cell and HeLa cell. To observe the activation of innate immunity by extracts of Mori radicis cortex, we estimated IL-6, IL-10, IL-12, TNF-${\alpha}$ from peritoneal macrophages. And we evaluated the activation of NK cell by using anti-asialo-GM1 serum. Results: We found that the administration of Mori radicis cortex extracts significantly inhibited tumor metastasis. In an in vitro cytotoxicity analysis, Mori radicis cortex affected tumor cell growth above specific concentration. Mori radicis cortex also stimulated peritoneal macrophage, which was followed by the production of various cytokines such as IL-6, IL-10, IL-12, TNF-${\alpha}$. The depletion of NK cells by anti-asialo GM1 serum partly abolished the inhibitory effect of Mori radicis cortex on tumor metastasis. Conclusion: Mori radicis cortex appears to have considerable activity on the anti-metastasis by activation of innate immunity.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.20
• /
• pp.9039-9043
• /
• 2014

There is a continuing need for innovative alternative therapies for liver cancer. DNA vaccines for hormone/growth factor immune deprivation represent a feasible and attractive approach for cancer treatment. We reported a preventive effect of a DNA vaccine based on six copies of the B cell epitope GRP18-27 with optimized adjuvants against H22 hepatocarcinoma. Vaccination with pCR3.1-VS-HSP65-TP-GRP6-M2 (vaccine) elicited much higher level of anti-GRP antibodies and proved efficacious in preventing growth of transplanted hepatocarcinoma cells. The tumor size and weight were significantly lower (p<0.05) in the vaccine subgroup than in the control pCR3.1-VS-TP-HSP65-TP-GRP6, pCR3.1-VS-TP-HSP65-TP-M2 or saline subgroups. In addition, significant reduction of tumor-induced angiogenesis associated with intradermal tumors of H22 cells was observed. These potent effects may open ways towards the development of new immunotherapeutic approaches in the treatment of liver cancer.

• Biomolecules & Therapeutics
• /
• v.20 no.1
• /
• pp.81-88
• /
• 2012

Histone deacetylases (HDACs) are enzymes involved in the remodelling of chromatin, and have a key role in the epigenetic regulation of gene expression. Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anti-cancer agents. In recent years, a number of structurally diverse HDAC inhibitors have been identifi ed and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. However, the underlying molecular mechanisms remain unclear. This study aimed at investigating the anti-tumor activity of various HDAC inhibitors, IN-2001, using T47D human breast cancer cells. Moreover, the possible mechanism by which HDAC inhibitors exhibit anti-tumor activity was also explored. In estrogen receptor positive T47D cells, IN-2001, HDAC inhibitor showed anti-proliferative effects in dose-and time-dependent manner. In T47D human breast cancer cells showed anti-tumor activity of IN-2001 and the growth inhibitory effects of IN-2001 were related to the cell cycle arrest and induction of apoptosis. Flow cytometry studies revealed that IN-2001 showed accumulation of cells at $G_2$/M phase. At the same time, IN-2001 treatment time-dependently increased sub-$G_1$ population, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with induction of cdk inhibitor expression. In T47D cells, IN-2001 as well as other HDAC inhibitors treatment significantly increased $p21^{WAF1}$ and $p27^{KIP1}$ expression. In addition, thymidylate synthase, an essential enzyme for DNA replication and repair, was down-regulated by IN-2001 and other HDAC inhibitors in the T47D human breast cancer cells. In summary, IN-2001 with a higher potency than other HDAC inhibitors induced growth inhibition, cell cycle arrest, and eventual apoptosis in human breast cancer possibly through modulation of cell cycle and apoptosis regulatory proteins, such as cdk inhibitors, cyclins, and thymidylate synthase.

• Herbal Formula Science
• /
• v.10 no.2
• /
• pp.113-126
• /
• 2002

Soamsan is known as an anti-cancer remedy in the traditional Korean Medicine. To enhance the synergic effects of anti-cancer activity of Soamsan, this study reconstituted the original components of Soamsan with a slight modification and produced a novel herbal remedy, namely Gamisoamsan. Extracts of Gamisoamsan inhibited the growth of cultured CT-26 cells, mouse colon adenocarcinoma, in a dose-dependent manner $(1\;to\;50{\mu}g/ml)$, and $ID_{50}$ was estimated approximately $16.7{\mu}g/ml$. Using tumor-bearing mouse model, in which was produced by subcutaneous injection of CT-26 cells ($1{\times}10^5$cells). the effects of Gamisoamsan on tumor growth and host survival were examined by evaluating tumor volume and increase in life span. When Gamisoamsan extracts in variable doses of 100, 200 and 500mg／kg body weight per day were orally administered to tumor-bearing mice, following results were obtained: Improvement in the hematological parameters following Gamisoamsan treatment such as hemoglobin contents, red blood cells and white blood cells of the tumor-bearing mice have been observed. Gamisoamsan treatment also showed a prolongation of life span and a reduction of tumor volume in the CT-26 tumor hosts. The results of the present study suggest that Gamisoamsan extracts has a potential anti-tumor activity and may be an useful remedy to prevent and／or treat cancer.

• The Journal of Korean Medicine
• /
• v.25 no.4
• /
• pp.79-89
• /
• 2004

Saussurea lappa and Taraxacum mongolicum have been used for herbal medicinal treatments against cancers in East Asia. We performed this study to understand the molecular basis underlying the anti-tumor effects of two herbs and analyzed the effects of these medicinal herbs on proliferation and on expression of cell growth/apoptosis related molecules by using an AGS gastric cancer cell line. The treatments of Saussurea lappa dramatically reduced cell viabilities in a dose and time-dependent manner, but Taraxacum mongolicum did not. FACS analysis and Annexin V staining assay also showed that Saussurea lappa induces apoptotic cell death of AGS. Expression analyses via RT-PCR and Western blots revealed that Saussurea lappa increased expression of the p53 and its downstream effector p21/sup Waf1/, and that the both increased expression of apoptosis related Bax and cleavage of active caspase-3 protein. We also confirmed the translocation of Bax to mitochondria Collectively, our data demonstrate that Saussurea lappa induces growth inhibition and apoptosis of human gastric cancer cells, and these effects are correlated with down- and up-regulation of growth-regulating apoptotic and tumor suppressor genes, respectively.

• BMB Reports
• /
• v.50 no.6
• /
• pp.283-284
• /
• 2017

Single cell transcriptome analysis is a powerful tool for defining cell types or sub-populations within a heterogeneous bulk population. Tumor-associated microenvironment is a complex ecosystem consisting of numerous cell types that support tumor growth, angiogenesis, immune evasion, and metastasis. With the success of checkpoint inhibitors targeting the immune cell compartment, tumor microenvironment is emerging as a potential anti-cancer target, and understanding it has become an imminent subject in cancer biology.

• Journal of Microbiology and Biotechnology
• /
• v.25 no.9
• /
• pp.1485-1492
• /
• 2015

Makgeolli is a traditional wine in Korea and has been traditionally believed to exhibit health benefits. However, the inhibitory effect of dealcoholized makgeolli (MK) on cancer has never been investigated scientifically. In this study, MK exhibited an anti-angiogenic effect by inhibiting tube formation in human umbilical vein endothelial cells, without cytotoxicity. Treatment with MK reduced the proliferation of AGS human gastric adenocarcinoma cells in a dose-dependent manner and increased the sub-G1 population. Next, we evaluated whether MK could induce apoptosis in AGS cells by using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay or Annexin V method. Treatment with MK at 500 and 1,000 μg/ml increased the number of TUNEL-positive AGS cells. Under the same conditions, MK-treated (500 and 1,000 μg/ml) cells showed significant induction of early or late apoptosis, compared with untreated cells (no induction). In addition, MK also induced phosphatase and tensin homolog (PTEN) expression in AGS cells. However, p53 expression in AGS cells was not changed by MK treatment. Furthermore, MK at 500 mg/kg·d reduced the tumor size and volume in AGS tumor xenografts. Taken together, MK may be useful for the prevention of cancer cell growth.

• Biomedical Science Letters
• /
• v.25 no.4
• /
• pp.398-406
• /
• 2019

Cancer immunotherapy using gene-modified tumor cells is safe and customized cancer treatment method. In this study, we made gene-modified tumor cells by transferring costimulatory molecules, 4-1BBL and OX40L, into tumor cells using lentivirus vector, and identified anti-cancer effect of gene-modified tumor cells in CT26 mouse colorectal tumor model. We construct pLVX-puro-4-1BBL, -OX40L vector for lentivirus production and optimized the transfection efficiency and transduction efficiency. The transfection efficiency is maximal at DNA:cationic polymer = 1:0.5 and DNA 2 ㎍ for lentivirus production. Then, the lentiviral including 4-1BBL and OX40L was used to deliver CT26 mouse tumor cells to establish optimal delivery conditions according to the amount of virus. The transduction efficiency is maximal at 500 μL volume of lentiviral stock without change in cell shape or growth rate. CT26-4-1BBL, CT26-OX40L significantly inhibited the tumor growth compare with CT26-WT or CT26-β-gal cell line. These data showed the possibility the use of genetically modified tumor cells with costimulatory molecule as cancer immunotherapy agent.

• Journal of Microbiology and Biotechnology
• /
• v.23 no.9
• /
• pp.1327-1338
• /
• 2013

The humanized anti-hepatocyte growth factor (HGF) monoclonal antibody (mAb) YYB-101 is a promising therapeutic candidate for treating various cancers. In this study, we developed a bioprocess for large-scale production of YYB-101 and evaluated its therapeutic potential for tumor treatment using a xenograft mouse model. By screening diverse chemically defined basal media formulations and by assessing the effects of various feed supplements and feeding schedules on cell growth and antibody production, we established an optimal medium and feeding method to produce 757 mg/l of YYB-101 in flask cultures, representing a 7.5-fold increase in titer compared with that obtained under non-optimized conditions. The optimal dissolved oxygen concentration for antibody production was 70% $pO_2$. A pH shift from 7.2 to 7.0, rather than controlled pH of either 7.0 or 7.2, resulted in productivity improvement in 5 L and 200 L bioreactors, yielding 737 and 830 mg/ml of YYB-101, respectively. The YYB-101 mAb highly purified by affinity chromatography using a Protein A column and two-step ion exchange chromatography effectively neutralized HGF in a cell-based assay and showed potent tumor suppression activity in a mouse xenograft model established with human glioblastoma cells.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.22
• /
• pp.9667-9672
• /
• 2014

Background: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. Materials and Methods: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-${\alpha}$ (IFN-${\alpha}$) on the ligands of NK and T cells was assessed by flow cytometry. Results: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) may be a potential strategy for treating pancreatic adenocarcinoma.