• Molecules and Cells
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• v.28 no.6
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• pp.553-558
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• 2009

In the periphery, a galectin-1 receptor, CD7, plays crucial roles in galectin-1-mediated apoptosis of activated T-cells as well as progression of T-lymphoma. Previously, we demonstrated that $NF-{\kappa}B$ downregulated CD7 gene expression through the p38 MAPK pathway in developing immature thymocytes. However, its regulatory pathway is not well understood in functional mature T-cells. Here, we show that CD7 expression was downregulated by Twist2 in Jurkat cells, a human acute T-cell lymphoma cell line, and in EL4 cells, a mature murine T-cell lymphoma cell line. Furthermore, ectopic expression of Twist2 in Jurkat cells reduced galectin-1-induced apoptosis. While full-length Twist2 decreased CD7 promoter activity, a C-terminal deletion form of Twist2 reversed its inhibition, suggesting an important role of the C-terminus in CD7 regulation. In addition, CD7 expression was enhanced by histone deacetylase inhibitors such as trichostatin A and sodium butyrate, which indicates that Twist2 might be one of candidate factors involved in histone deacetylation. Based on these results, we conclude that upregulation of Twist2 increases the resistance to galectin-1-mediated-apoptosis, which may have significant implications for the progression of some T-cells into tumors such as Sezary cells.

• Molecules and Cells
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• v.41 no.11
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• pp.971-978
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• 2018

The stem cell factor (SCF)/c-KIT axis plays an important role in the hematopoietic differentiation of human pluripotent stem cells (hPSCs), but its regulatory mechanisms involving microRNAs (miRs) are not fully elucidated. Here, we demonstrated that supplementation with SCF increases the hematopoietic differentiation of hPSCs via the interaction with its receptor tyrosine kinase c-KIT, which is modulated by miR-221 and miR-222. c-KIT is comparably expressed in undifferentiated human embryonic and induced pluripotent stem cells. The inhibition of SCF signaling via treatment with a c-KIT antagonist (imatinib) during hPSC-derived hematopoiesis resulted in reductions in the yield and multi-lineage potential of hematopoietic progenitors. We found that the transcript levels of miR-221 and miR-222 targeting c-KIT were significantly lower in the pluripotent state than they were in terminally differentiated somatic cells. Furthermore, suppression of miR-221 and miR-222 in undifferentiated hPSC cultures induced more hematopoiesis by increasing c-KIT expression. Collectively, our data implied that the modulation of c-KIT by miRs may provide further potential strategies to expedite the generation of functional blood cells for therapeutic approaches and the study of the cellular machinery related to hematologic malignant diseases such as leukemia.

• Korean Journal of Pharmacognosy
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• v.37 no.3
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• pp.190-195
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• 2006

Obesity is associated with a number of pathological disorders such as non-insulin-dependent diabetes, hypertension, hyperlipidemia, and cardiovascular diseases. Bangpoongtongsungsankamibang (BTSK) has been widely used in the oriental medicine for the treatment of several diseases associated with inflammatory abnormalities in cardiovascular and nervous system. The BTSK is the modified prescription of Bangpoongtongsungsankamibang in which sea tangle (Laminaria japonica) were added. This study was carried out to detemine the anti-obestic effects of BTSK. Pretreatment with the BTSK at daily dose of 100 or 200 mg/kg (p.o.) far 4 weeks reduced serum triglyceride, total cholesterol contents in rat induced by Poloxamer-407 or Triton WR-1339, respectively. Furthermore, post-treatment with BTSK far four weeks also inhibited body weight gain, adipose tissue mass and hyperlipidemia induced by the high fat diet for six weeks. The BTSK shifted serum total-, HDL- and LDL-cholesterol levels toward the values of normal group, suggesting that BTSK has hypolipldemlc effects. The rats fed BTSK reduced lipid peroxide and hydroxy radical in the rat blood and increased superoxide dismutase (SOD) activity compared to the control group. Taken together, these results superoxide that BTSK improve hyperlidemia and obesity via the upregulation of anti-oxidative mechanism.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7575-7582
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• 2015

Cyclin E, a key coordinator of the G1 to S transition in the cell cycle, may be deregulated in several malignancies, including breast cancer. The most significant aberration in cyclin E is its elastase mediated proteolytic cleavage into tumor specific low molecular weight isoforms (LMW-Es). LMW-Es are biochemically hyperactive and biologically drive tumorigenesis in transgenic mouse models. Additionally, expression of LMW-Es has been correlated with poor survival in breast cancer cases. Here we determine whether expression of LMW-Es in a breast cancer cell line that is naturally devoid of these deregulated forms would alter their progression through each phase of the cell cycle. The results revealed that LMW-Es expression resulted in an increased doubling time, concomitant with a predominant increase in the population in the S phase of the cell cycle. Moreover, downregulation of p53 in LMW-Es cells resulted in additional shortening of the doubling time and enrichment of cells in the S and G2/M phases of the cell cycle. Furthermore, expression of LMW-Es sensitized cells to ${\beta}$-estradiol (E2) mediated growth and changed expression patterns of estrogen receptor and Bcl-2. Intriguingly, expression of LMW-Es could surpass anti-apoptotic effects raised by p53 upregulation. Taken together these studies suggest that overexpression of LMW-Es in collaboration with p53 loss results in altered g rowth properties of MCF-7 cells, enhancing the oncogenic activity of these ER positive breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6369-6374
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• 2012

Vitexicarpin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone), a polymethoxyflavone isolated from Viticis Fructus (Vitex rotundifolia Linne fil.), has long been used as an anti-inflammatory herb in traditional Chinese medicine. It has also been reported that vitexicarpin can inhibit the growth of various cancer cells. However, there is no report elucidating its effect on human prostate carcinoma cells. The aim of the present study was to examine the apoptotic induction activity of vitexicarpin on PC-3 cells and molecular mechanisms involved. MTT studies showed that vitexicarpin dose-dependently inhibited growth of PC-3 cells with an $IC_{50}{\sim}28.8{\mu}M$. Hoechst 33258 staining further revealed that vitexicarpin induced apoptotic cell death. The effect of vitexicarpin on PC-3 cells apoptosis was tested using prodium iodide (PI)/Annexin V-FITC double staining and flow cytometry. The results indicated that vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase. Furthermore, our study demonstrated that vitexicarpin induction of PC-3 cell apoptosis was associated with upregulation of the proapoptotic protein Bax, and downregulation of antiapoptotic protein Bcl-2, release of Cytochrome c from mitochondria and decrease in mitochondrial membrane potential. Our findings suggested that vitexicarpin may become a potential leading drug in the therapy of prostate carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1425-1430
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• 2012

Cyclin L2 is a novel member of the cyclin family, recently implicated in the regulation of cell cycle progression and/or transcriptional regulation. The present study was undertaken to investigate the effects of overexpression on tumor cell growth and chemosensitivity in human gastric cells in vitro. Cyclin L2 was transfected into human gastric cancer cell line BCG823 and expressed with a mammalian expression vector pcDNA3.1. The effects and mechanisms of cyclin L2 on cell growth, cell cycling and apoptosis were studied. Compared to control vectors, overexpression of cyclin L2 inhibited the growth of BCG823 cells and enhance their chemosensitivity to fluorouracil, docetaxel and cisplatin. The anti-proliferative effects of cyclin L2 could be due to G0/G1 arrest and apoptosis. Cyclin L2 induced G0/G1 arrest and apoptosis involved upregulation of caspase-3 and down regulation Bcl-2 and survivin. The results indicated that overexpression of cyclin L2 protein may promote efficient growth inhibition and enhance chemosensitivity to chemotherapeutic agents in human gastric cancer cells by inducing G0/G1 cell cycle arrest and apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7473-7478
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• 2014

Cholangiocarcinoma (CCA) is a fatal cancer with poor prognosis and less than 10% of CCA patients can be offered surgical cure. Conventional chemotherapy results in unfavorable outcomes. At present, plant-derived compounds are gaining interest as potential cancer therapeutics, particularly for treatment-refractory cancers. In this study, antitumor activity of tiliacorinine, the major alkaloid isolated from a tropical plant, on CCA was first demonstrated. Antiproliferative effects of tiliacorinine on human CCA cell lines were investigated using SRB assays. Acridine orange/ethidium bromide staining, flow cytometric analysis and DNA laddering assays were used for apoptotic determination. Apoptosis-related proteins were verified by Western blotting and antitumor activity of tiliacorinine in vivo was demonstrated in CCA xenografted mice. Tiliacorinine significantly inhibited proliferation of human CCA cell lines with $IC_{50}$ $4.5-7{\mu}M$ by inducing apoptosis through caspase activation, upregulation of BAX, and downregulation of $Bcl_{xL}$ and XIAP. Tiliacorinine considerably reduced tumor growth in CCA xenografted mice. These results demonstrated antitumor effects of tiliacorinine on human CCA in vitro and in vivo. Tiliacorinine may be an effective agent for CCA treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7037-7041
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• 2014

Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers.

• Journal of dental hygiene science
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• v.15 no.4
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• pp.488-494
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• 2015

A recent report showed that nuclear factor of activated T cell (NFATc) 1 is a member of the NFAT family and is strictly implicated osteoblast differentiation and bone formation. Furthermore, the precise expression and function of NFATc1 in periodontal tissue remains unclear. Therefore, the purpose of this study was to investigate the function of NFATc1 in osteoblastic differentiation, and the underlying mechanism regulating periodontal regeneration in human periodontal ligament cells (hPDLCs). NFATc1 messenger RNA (mRNA) and protein levels were accessed by reverse transcription-polymerase chain reaction (RT-PCR) and western blot assay, respectively. Cell proliferation determined using MTT assay. Differentiation was evaluated by alkaline phosphatase activity and formation of calcium nodule with alizarin red S staining. The mRNA expression of osteoblastic differentiation related genes were examined by RT-PCR. Marked upregulation of NFATc1 mRNA and protein was observed in cells grown in osteogenic medium (OS). NFATc1 transactivation was detected in hPDLCs that had been incubated in OS for 14 days. Treatment with $10{\mu}M$ cyclosporine A (CsA), a known calcineurin inhibitor, reduced the proliferation of hPDLCs, while $5{\mu}M$ CsA had no effect. Inhibition of the calcineurin/NFATc1 pathway by CsA, attenuated OS-induced osteoblastic differentiation in hPDLCs. In summary, this study demonstrates for the first time that NFATc1 plays a key role in osteoblastic differentiation of hPDLCs and activation of NFATc1 could provide a novel mechanism for periodontal bone regeneration.

• Animal cells and systems
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• v.16 no.5
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• pp.391-399
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• 2012

We cloned cDNA-encoding arginine vasotocin (AVT) from the brain of the cinnamon clownfish Amphiprion melanopus, and that was predicted to encode a protein of 153 amino acids. We examined changes in the expression of AVT mRNA in the brain and arginine vasotocin receptor (AVTR) mRNA and osmotic stress transcription factor 1 (OSTF1) mRNA in the gills of the cinnamon clownfish using quantitative real-time PCR in an osmotically changing environment (seawater (35 psu) ${\rightarrow}$ brackish water (BW, 17.5 psu) and BW with prolactin [PRL]). The expression of AVT, AVTR, and OSTF1 mRNA in the brain and gills increased after transfer to BW, and the expression was repressed by PRL treatment. AVT-immunoreactive cells were almost consistently observed in the telencephalon. The plasma $Na^+$ and $Cl^-$ levels decreased in BW, but the level of this parameter increased in BW with PRL treatme during salinity change. These results suggest that AVT, AVTR, and OSTF1 play important roles in hormonal regulation in osmoregulation organs, and that PRL improves the hyperosmoregulatory ability of cinnamon clownfish in BW environment.