• Reproductive and Developmental Biology
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• 제36권4호
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• pp.275-281
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• 2012

Embryonic stem cell-preconditioned microenvironment is important for cancer cells properitities by change cell morphology and proliferation. This microenvironment induces cancer cell reprogramming and results in a change in cancer cell properties such as differentiation and migration. The cancer microenvironment affects cancer cell proliferation and growth. However, the mechanism has not been clarified yet. Using the ES-preconditioned 3-D microenvironment model, we provide evidence showing that the ES microenvironment inhibits proliferation and reduces oncogenic gene expression. But ES microenvironment has no effect on telomerase activity, cell viability, cellular senescence, and methylation on Oct4 promoter region. Furthermore, methylation of Nanog was increase on ES-preconditioned microenvironment and supports results that no difference on RNA expression levels. Taken together, these results demonstrated that in the ES-preconditioned 3-D microenvironment is a crucial role for cancer cell proliferation not senescence.

• IMMUNE NETWORK
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• 제23권5호
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• pp.41.1-41.21
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• 2023

CD4 and CD8 T cells are key players in the immune response against both pathogenic infections and cancer. CD4 T cells provide help to CD8 T cells via multiple mechanisms, including licensing dendritic cells (DCs), co-stimulation, and cytokine production. During acute infection and vaccination, CD4 T cell help is important for the development of CD8 T cell memory. However, during chronic viral infection and cancer, CD4 helper T cells are critical for the sustained effector CD8 T cell response, through a variety of mechanisms. In this review, we focus on T cell responses in conditions of chronic Ag stimulation, such as chronic viral infection and cancer. In particular, we address the significant role of CD4 T cell help in promoting effector CD8 T cell responses, emerging techniques that can be utilized to further our understanding of how these interactions may take place in the context of tertiary lymphoid structures, and how this key information can be harnessed for therapeutic utility against cancer.

• Journal of Ginseng Research
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• 제44권2호
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• pp.282-290
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• 2020

Background: Ginseng is a commonly used herbal medicine in treating various medical conditions. Chronic gut inflammation is a recognized factor for the development of colorectal cancer (CRC). In this project, Asian ginseng berry polysaccharide preparations were used to assess their effects on CRC and related immune regulation mechanisms. Methods: Ginseng berry polysaccharide extract (GBPE) and purified ginseng berry polysaccharide portion (GBPP) were used to evaluate their activities on human HCT-116 and HT-29 CRC cell proliferation. Interleukin-8 secretion analysis was performed on HT-29 cells. Naive CD4 cell isolation and T-helper cell differentiation were performed and determined using flow cytometry for Th1 and Treg in addition to cell cycle and apoptotic investigation. Results: GBPE and GBPP significantly inhibited interleukin-8 secretion and cancer cell proliferation, inhibited CD4⁺IFN-γ⁺ cell (Th1) differentiation, and decreased CD4⁺FoxP3⁺ cell (Treg) differentiation. Compared to the GBPE, GBPP showed more potent antiinflammatory activities on the malignant cells. This is consistent with the observation that GBPP can also inhibit Th1-cell differentiation better, suggesting that it has an important role in antiinflammation, whereas Treg cells hinder the body's immune response against malignancies. Supported by cell cycle and apoptosis data, GBPE and GBPP, at various degrees, remarkably enhanced the anticancer activities of 5-fluorouracil. Conclusion: Data from this project suggested that Asian ginseng berry potentially has clinical utility in managing enteric inflammation and suppressing CRC through immunomodulation mechanisms.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.91.2-91.2
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• 2003

Cyclin-dependent kinases (CDKs) regulate the cell division cycle, apoptosis, transcription and differentiation. Inhibition of CDK is a promising target in development of anti-cancer agents. An indirubin analog (AGM01l), a CDK inhibitor, is a synthetic compound that inhibits human cancer cell growth in vitro. AGM01l showed a potent cytotoxicity in cultured human cancer cell lines (IC$\sub$50/ = 5.43 ${\mu}$M for A549, human colon cancer cell; IC$\sub$50/ = 1.21 ${\mu}$M for SNU-638, human stomach cancer cell; IC$\sub$50/ 9.23 ${\mu}$M for HL-60, human leukemia cell). (omitted)

• Molecules and Cells
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• 제28권1호
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• pp.7-12
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• 2009

Gliomas, much like other cancers, are composed of a heterogeneous mix of neoplastic and non-neoplastic cells that include both native and recruited cells. There is extensive diversity among the tumor cells, with differing capacity for In vitro and in vivo growth, a property intimately linked to the cell's differentiation status. Those cells that are undifferentiated, self-renewing, with the capacity for developing tumors (tumorigenic) cells are designated by some as cancer stem cells, because of the stem-like properties. These cells may be a critical therapeutic target. However the exact identity and cell(s) of origin of the socalled glioma cancer stem cell remain elusive. Here we review the current understanding of glioma cancer stem cell biology.

• Animal cells and systems
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• 제14권4호
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• pp.261-266
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• 2010

PC12 cells were differentiated into the cells of chromaffin phenotype by butyrate treatment. Cells were aggregated and formed tight cell adhesion. To investigate the molecular change in this differentiation, we examined expression levels of cell adhesion proteins and extracellular proteins during butyrate induced-differentiation of PC12 cells. Integrin ${\beta}1$, integrin ${\alpha}7$, E cadherin, VCAM, collagen-I, fibronectin, desmoglein and connexin were increased during differentiation. The levels of clusterin and secreted clusterin were also increased. These increased levels of cell adhesion proteins and extracellular proteins appear to induce cell aggregation and tight cell adhesion. The levels of p21, p27 and p16 were increased probably because of differentiation-related growth arrest during differentiation. Prolonged incubation of butyrate up to 1 day was required for differentiation. Signal transduction pathways for this differentiatiom could not be identified since various inhibitors had no effect. The results showed that butyrateinduced differentiation of PC12 cells to chromaffin cells involves tight cell adhesion and induction of extracellular proteins and cell adhesion proteins.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.607-611
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• 2012

Non-toxic stimulation of dendritic cells (DCs), which are central immunomodulators, may aid the prevention of cancer. Furthermore, induction of apoptosis in cancer cells by anticancer agents contributes to the induction of DC maturation. We previously reported that extracts from $Pinus$ $parviflora$ Sieb. et Zucc pine cone and $Mucuna$ seed induce differentiation of mouse bone marrow cells into mature dendritic cells and also induce apoptosis in various human cancer cell lines. In the present study, we screened 31 kinds of edible beans with biological activity similar to that of extracts from pine cone and $Mucuna$ and found that the heat-stable extract from azuki bean ($Vigna$ $angula$) stimulated differentiation of bone marrow cells into immature DCs with the greatest efficacy. The level of IL-6 produced by sequential treatment of DCs with azuki extract and lipopolysaccharide was the highest among the examined beans. Azuki extract also inhibited the growth of human leukemia U937 cells, leading to induction of apoptosis. These results suggest that azuki bean and its extract are immunopotentiating foods that can be used as a dietary supplement for cancer prevention and immunotherapy.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.90-90
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• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47D and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 추계국제학술대회
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• pp.180-180
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• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER Positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47B and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

• Molecules and Cells
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• 제24권1호
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• pp.1-8
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• 2007

Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from $CD34^+$hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.