• 대한한의학회지
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• 제23권1호
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• pp.24-36
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• 2002

Objectives: The chemotherapeutic potential of Gagamgilgyung-tang for the treatment of human lung cancer, the antitumorigenic effects of Gagamgilgyung-tang on the proliferation and apoptosis of human lung cancer cell line A427 were investigated using molecular biological approaches, Methods: To determine Gagamgilgyung-tang concentrations which do not evoke cytotoxic damage to the cell line, cell viability was examined by MTT assay. To prove Gagamgilgyung-tang's antitumorigenic potential to human lung cancer, [3H]thymidine incorporation assay, trypan blue exclusion and Cpp32 protease activity assays and quantitative RT-PCR analysis were examined. Results: While A427 cells treated with $0.1-2.0{\mu\textrm{g}}/ml$ of Gagamgilgyung-tang showed no recognizable effect, marked reductions of cell viability were detected at concentrations over $5.0{\;}\mu\textrm{g}/ml$. DNA replication of A427 cells was inhibited by Gagamgilgyung-tang in a dose-dependent manner and Gagamgilgyung-tang induced the G1 cell cycle arrest through inhibition of DNA replication. Gagamgilgyung-tang triggered apoptotic cell death of A427 and enhanced the apoptotic sensitivity of the cells that were injured by a DNA damage-inducing chemotherapeutic drug etoposide. Gagamgilgyung-tang induces expression of growth-inhibiting genes such as p53 and p21/Wafl whereas it inhibited expression of growth-promoting genes such as c-Myc and Cyclin D1. Expression of a representative apoptosis-inducing gene Bax was also found to be induced by Gagamgilgyung-tang while apoptosis-suppressing Bcl-2 expression was not changed. Conclusions: Gagamgilgyung-tang could suppress the abnormal growth of tumor cells by suppressing the survival of genetically altered cells via induction of apoptosis. This study suggests that Gagamgilgyung-tang might have an antitumorigenic potential to human lung cancer cells, which might be associated with its growth-inhibiting and apoptosis-inducing properties.

• Molecules and Cells
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• 제39권4호
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• pp.330-336
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• 2016

Long non-coding RNAs (lncRNAs) are involved in multiple cellular events, as well as in tumorigenesis. Colon cance-rassociated transcript-1 (CCAT1) gene encodes an lncRNA whose over-activation was observed in an expanding list of primary human solid tumors and tumor cell lines, however its biological roles in acute myeloid leukaemia (AML) has not been reported yet at present. In this study, the aberrant upregulation of CCAT1 was detected in French-American-British M4 and M5 subtypes of adult AML patients. By gain- and loss-of-function analysis, we determined that CCAT1 repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155. Accordingly, a significant decrease in miR-155 level was detected in AML patients. Reintroduction of miR-155 into HL-60 cells restored monocytic maturation and repressed cell proliferation. Furthermore, CCAT1 could up-regulated c-Myc via its competing endogenous RNA (ceRNA) activity on miR-155. In conclusion, these results revealed new mechanism of lncRNA CCAT1 in AML development, and suggested that the manipulation of CCAT1 expression could serve as a potential strategy in AML therapy.

• Journal of Microbiology
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• 제45권3호
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• pp.187-192
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• 2007

REOviruses (Respiratory Enteric Orphan viruses) are ubiquitous, non-enveloped viruses containing 10 segments of double-stranded RNA (dsRNA) as their genome. They are common isolates of the respiratory and gastrointestinal tract of humans but are not associated with severe disease and are therefore considered relatively benign. An intriguing characteristic of reovirus is its innate oncolytic potential, which is linked to the transformed state of the cell. When immortalized cells are transfected in vitro with activated oncogenes such as Ras, Sos, v-erbB, or c-myc, they became susceptible to reovirus infection and subsequent cellular lysis, indicating that oncogene signaling pathways are exploited by reovirus. This observation has led to the use of the virus in clinical trials as an anti-cancer agent against oncogenic tumors. In addition to the exploitation of oncogene signaling, reovirus may further utilize host immune responses to enhance its antitumor activity in vivo due to its innate interferon induction ability. Reovirus is, however, not entirely benign to immunocompromised animal models. Reovirus causes so-called "black feet syndrome" in immunodeficient mice and can also harm neonatal animals. Because cancer patients often undergo immunosuppression due to heavy chemo/radiation-treatments or advanced tumor progression, this pathogenic response may be a hurdle in virus-based anticancer therapies. However, a genetically attenuated reovirus variant derived from persistent reovirus infection of cells in vitro is able to exert potent anti-tumor activity with significantly reduced viral pathogenesis in immunocompromised animals. Importantly, in this instance the attenuated, reovirus maintains its oncolytic potential while significantly reducing viral pathogenesis in vivo.

• IMMUNE NETWORK
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• 제11권6호
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• pp.348-357
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• 2011

Background: N-myc downstream-regulated gene 2 (NDRG2), a member of a newly described family of differentiation-related genes, has been characterized as a regulator of dendritic cells. However, the role of NDRG2 on the expression and activation of transcription factors in blood cells remains poorly understood. In this study, we investigated the effects of NDRG2 overexpression on GATA-1 expression in PMAstimulated U937 cells. Methods: We generated NDRG2-overexpressing U937 cell line (U937-NDRG2) and treated the cells with PMA to investigate the role of NDRG2 on GATA-1 expression. Results: NDRG2 overexpression in U937 cells significantly induced GATA-1 expression in response to PMA stimulation. Interestingly, JAK2/STAT and BMP-4/Smad pathways associated with the induction of GATA-1 were activated in PMA-stimulated U937-NDRG2 cells. We found that the inhibition of JAK2 activation, but not of BMP-4/Smad signaling, can elicit a decrease of PMA-induced GATA-1 expression in U937-NDRG2 cells. Conclusion: The results reveal that NDRG2 promotes the expression of GATA-1 through activation of the JAK2/STAT pathway, but not through the regulation of the BMP-4/Smad pathway in U937 cells. Our findings further suggest that NDRG2 may play a role as a regulator of erythrocyte and megakaryocyte differentiation during hematopoiesis.

• 폴리머
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• 제28권3호
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• pp.218-224
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• 2004

고분자 생체재료에서 세포부착과 성장은 재료의 적심성, 화학구조, 표면전하 및 거칠기 등의 표면 성질에 의존한다. 본 연구에서는 저밀도 폴리에틸렌 필름 (LDPE)의 표면 적심성과 골수유래 줄기세포의 증식 및 성장성을 측정하기 위하여 플라즈마 처리를 실시하였으며 개질된 필름 표면의 특성을 조사하였다. 또한 LDPE 필름에서의 세포부착과 증식률은 세포수 관찰과 역전사 중합효소 연쇄반응으로 확인하였다. 표면성질의 하나인 물 접촉각 측정 결과 플라즈마 처리 시간이 길어짐에 따라 필름표면의 접촉각이 감소하였으며 암형성 유전자와 암억제 유전자의 발현률이 60∼70$^{\circ}$ 사이에서 높음을 확인할 수 있었다. 또한 세포수 관찰을 통해 접촉각이 60∼70$^{\circ}$인 표면에서 세포 증식률이 우수하여 표면성질이 세포의 성장과 분화에 중요함을 확인하였다.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.8.1-8.12
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• 2018

FAM46B is a member of the family with sequence similarity 46. Little is known about the expression and functional role (s) of FAM46B in prostate cancer (PC). In this study, the expression of FAM46B expression in The Cancer Genome Atlas, GSE55945, and an independent hospital database was measured by bioinformatics and real-time PCR analysis. After PC cells were transfected with siRNA or a recombinant vector in the absence or presence of a ${\beta}$-catenin signaling inhibitor (XAV-939), the expression levels of FAM46B, C-myc, Cyclin D1, and ${\beta}$-catenin were measured by western blot and realtime PCR. Cell cycle progression and cell proliferation were measured by flow cytometry and the CCK-8 assay. The effects of FAM46B on tumor growth and protein expression in nude mice with PC tumor xenografts were also measured. Our results showed that FAM46B was downregulated but that ${\beta}$-catenin was upregulated in patients with PC. FAM46B silencing promoted cell proliferation and cell cycle progression in PC, which were abrogated by XAV-939. Moreover, FAM46B overexpression inhibited PC cell cycle progression and cell proliferation in vitro and tumor growth in vivo. FAM46B silencing promoted ${\beta}$-catenin protein expression through the inhibition of ${\beta}$-catenin ubiquitination. Our data clearly show that FAM46B inhibits cell proliferation and cell cycle progression in PC through ubiquitination of ${\beta}$-catenin.

• Asian Pacific Journal of Cancer Prevention
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• 제18권11호
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• pp.2919-2923
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• 2017

Objective: Anthocyanins belong to a class of flavonoids, exhibiting antioxidant and anti-inflammatory actions have been reported to have anti-cancer effects. Here, we investigated whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in human lung cancer A549 cells, which are critically involved in cancer metastasis. Methods: We used anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) which has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers. We have performed cell proliferation assays, cell invasion assay, gelatin zymography, wound healing assay and western blotting to examine whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in A549 cells. Result: AIMs did not inhibit cancer cell proliferation on A549 cells. Also, AIMs suppressed cancer migration, and invasion by supressing MMP-2 and MMP-9 expression. The Immuno-blotting results also revealed that AIMs suppressed the proteins involved in cancer proliferation (COX-2, C-myc, cyclin D1), migration and invasion (MMP-2, MMP-9), anti-apoptosis (XIAP, and c-IAP2), adhesion and angiogenesis (ICAM-1, VEGF). Conclusion: This study demonstrates that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat inhibit cancer proliferation, cancer migration, and invasion that is involve in cancer-metastasis. This study provides evidence that AIMs might have anti-cancer effects on human lung cancer.

• Integrative Medicine Research
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• 제3권2호
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• pp.67-73
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• 2014

Background: The transcription factor signal transducer and activator of transcription 3 (Stat3)is constitutively activated in many human cancers. It promotes tumor cell proliferation,inhibits apoptosis, induces angiogenesis and metastasis, and suppresses antitumor hostimmune responses. Therefore, Stat3 has emerged as a promising molecular target for cancertherapies. In this study, we evaluated the Stat3-suppressive activity of 38 herbal medicinestraditionally used in Korea.Methods: Medicinal herb extracts in 70% ethanol were screened for their ability to suppressStat3 in the A549 human lung cancer cell line. A Stat3-responsive reporter assay system wasused to detect intracellular Stat3 activity in extract-treated cells, and Western blot analyseswere performed to measure the expression profiles of Stat3-regulated proteins.Results: Fifty percent of the 38 extracts possessed at least mild Stat3-suppressive activities(i.e., activity less than 75% of the vehicle control). Ethanol extracts of Bupleurum falcatumL., Taraxacum officinale Weber, Solanum nigrum L., Ulmus macrocarpa Hance, Euonymus alatusSieb., Artemisia capillaris Thunb., and Saururus chinensis (Lour.) Baill inhibited up to 75% of thevehicle control Stat3 activity level. A549 cells treated with these extracts also had reducedBcl-xL, Survivin, c-Myc, and Mcl-1 expression.Conclusion: Many medicinal herbs traditionally used in Korea contain Stat3 activity-suppressing substances. Because of the therapeutic impact of Stat3 inhibition, these resultscould be useful when developing novel cancer therapeutics from medicinal herbs.

• Molecules and Cells
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• 제45권6호
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• pp.425-434
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• 2022

The post-translational modification (e.g., phosphorylation) of estrogen receptor α (ERα) plays a role in controlling the expression and subcellular localization of ERα as well as its sensitivity to hormone response. Here, we show that ERα is also modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability and transactivity of ERα, which in turn promotes breast cancer development. The elevation of ufmylation via the knockdown of UFSP2 (the UFM1-deconjugating enzyme in humans) dramatically increases ERα stability by inhibiting ubiquitination. In contrast, ERα stability is decreased by the prevention of ufmylation via the silencing of UBA5 (the UFM1-activating E1 enzyme). Lys171 and Lys180 of ERα were identified as the major UFM1 acceptor sites, and the replacement of both Lys residues by Arg (2KR mutation) markedly reduced ERα stability. Moreover, the 2KR mutation abrogated the 17β-estradiol-induced transactivity of ERα and the expression of its downstream target genes, including pS2, cyclin D1, and c-Myc; this indicates that ERα ufmylation is required for its transactivation function. In addition, the 2KR mutation prevented anchorage-independent colony formation by MCF7 cells. Most notably, the expression of UFM1 and its conjugating machinery (i.e., UBA5, UFC1, UFL1, and UFBP1) were dramatically upregulated in ERα-positive breast cancer cell lines and tissues. Collectively, these findings implicate a critical role attributed to ERα ufmylation in breast cancer development by ameliorating its stability and transactivity.

• Genomics & Informatics
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• 제20권3호
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• pp.27.1-27.13
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• 2022

Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck malignancy, with frequent cervical lymph-node metastasis, leading to a poor prognosis in OSCC patients. The present study aimed to identify potential markers, including microRNAs (miRNAs) and genes, significantly involved in the etiology of early-stage OSCC. Additionally, the main OSCC's dysregulated Gene Ontology annotations and significant signaling pathways were identified. The dataset GSE45238 underwent multivariate statistical analysis in order to distinguish primary OSCC tissues from healthy oral epithelium. Differentially expressed miRNAs (DEMs) with the criteria of p-value < 0.001 and |Log2 fold change| > 1.585 were identified in the two groups, and subsequently, validated targets of DEMs were identified. A protein interaction map was constructed, hub genes were identified, significant modules within the network were illustrated, and significant pathways and biological processes associated with the clusters were demonstrated. Using the GEPI2 database, the hub genes' predictive function was assessed. Compared to the healthy controls, main OSCC had a total of 23 DEMs. In patients with head and neck squamous cell carcinoma (HNSCC), upregulation of CALM1, CYCS, THBS1, MYC, GATA6, and SPRED3 was strongly associated with a poor prognosis. In HNSCC patients, overexpression of PIK3R3, GIGYF1, and BCL2L11 was substantially correlated with a good prognosis. Besides, "proteoglycans in cancer" was the most significant pathway enriched in the primary OSCC. The present study results revealed more possible mechanisms mediating primary OSCC and may be useful in the prognosis of the patients with early-stage OSCC.