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Publications (54)
Induction of differentiation sensitizes chronic myeloid leukemia (CML) cells to the BCR-ABL inhibitor imatinib by mechanisms that remain unknown. We previously identified the BCR-ABL downstream effector CD69 which inhibits imatinib-induced CML cell differentiation. Herein, we found that the erythroid differentiation inducers activin A and aclacinom...
Background: Histone deacetylase (HDAC) inhibitors have emerged as a new class of anti-tumor agents for various types of tumors, including glioblastoma.
Methods and results: We found that a novel HDAC inhibitor, MPT0B291, significantly reduced the cell viability and increased cell death of human and rat glioma cell lines, but not in normal astrocyte...
In the present study, we investigated the role of PKR‐like endoplasmic reticular kinase (PERK), an endoplasmic reticulum (ER) stress kinase, in endothelin 1 (ET‐1)‐ and thrombin‐induced pulmonary fibrosis (PF), and the preventive effects of curcumin (CUR). Using the human embryonic WI‐38 lung fibroblast cell line, ET‐1 and thrombin induced the expr...
Paclitaxel (PTX) is a common regimen used to treat patients with ovarian cancer. Although approximately 60% of ovarian cancer patients exhibit a pathologic complete response (pCR), approximately 40% of patients appear to be insensitive to PTX adjuvant therapy. Thus, identifying a useful biomarker to predict pCR would be of great help to ovarian can...
Nilotinib (AMN), a second‐generation tyrosine kinase inhibitor, induces apoptosis in various cancer cells, and our recent study showed that AMN effectively reduced the viability of human ovarian cancer cells via mitochondrion‐dependent apoptosis. The effect of AMN in the melanogenesis of melanoma cells is still unclear. In the present study, we fou...
We previously synthesized new tubulin inhibitors, MPT0B169 and MPT0B002, which induced growth inhibition and apoptosis in leukemia cells. However, their effects on solid tumor cells have not been determined. In this study, we investigated the effects of MPT0B169 and MPT0B002 on glioblastoma, breast, lung, and colorectal cancer (CRC) cell lines. A c...
Chronic myeloid leukemia (CML) is caused by a constitutively active BCR‐ABL tyrosine kinase. Tyrosine kinase inhibitors (TKIs) imatinib and its derivatives represent a breakthrough for CML therapy, but the use of TKI alone is ineffective for many CML patients. CD69, an early activation marker of lymphocytes, participates in immune and inflammatory...
[This corrects the article DOI: 10.1371/journal.pone.0148093.].
[This corrects the article DOI: 10.1371/journal.pone.0063613.].
[This corrects the article DOI: 10.1371/journal.pone.0061939.].
[This corrects the article DOI: 10.1155/2015/678487.].
Osthole, an active component of Chinese herbal medicines, reportedly possesses various pharmacological properties and has potential therapeutic applications. This study explored the anti-allergic effects of osthole in asthmatic mice and investigated the immunomodulatory actions of osthole on dendritic cells (DCs) and T cells. Herein, we show that o...
Chronic myeloid leukemia (CML) is a hematopoietic malignancy caused by the constitutive activation of Bcr-Abl tyrosine kinase. The Bcr-Abl inhibitor imatinib and other second-generation tyrosine kinase inhibitors such as dasatinib and nilotinib have remarkable efficacy in CML treatment. However, gene mutation-mediated drug resistance remains a crit...
Imatinib, a Bcr-Abl-specific inhibitor, is effective for treating chronic myeloid leukemia (CML), but drug resistance has emerged for this disease. In this study, we synthesized a novel tubulin polymerization inhibitor, MPT0B206 (N-[1-(4-methoxy-benzenesulfonyl)-2,3-dihydro-1H-indol-7-yl]-formamide), and demonstrated its apoptotic effect and mechan...
Chronic myeloid leukemia (CML) is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and thei...
Acute myeloid leukemia (AML) is a hematological malignant disorder. AML cells are not susceptible to chemotherapeutic drugs because of their multidrug resistance (MDR). Antitubulin agents are currently employed in cancer treatments; however, drug resistance results in treatment failures because of MDR1 expressing cancer cells. We previously synthes...
This study investigated the immunomodulatory effects of ferulic acid (FA) on antigen-presenting dendritic cells (DCs) in vitro and its antiallergic effects against ovalbumin- (OVA-) induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation induced a high level of inter...
DCs were treated with 5 to 5000 uM FA for 72 h and cell viability was detected by MTT assay. Because FA showed no cytotoxicity at concentrations up to 500 uM in DCs, we used up to 400 uM FA for the rest of the experiments.
TNF‐α and activin A suppresses and induces erythroid gene expression, respectively. Previous studies showed that TNF‐α up‐regulates expression of CD69 in erythroblast K562 cells by an erythropoiesis suppressor NF‐κB. In this study, we investigated the role of CD69 in promoter activity and expression of erythroid genes, α‐globin and ζ‐globin, in res...
Background: The activation of the tumor necrosis factor-alpha (TNF-α)/nuclear factor kappa B (NF-κB) pathway inhibits the expression of erythroid genes, whereas activin A, a member of the transforming growth factor-β superfamily, induces erythroid differentiation. The effect of TNF-α on activin A-induced erythroid gene expression has not been eluci...
Interferon (IFN)-γ is a proinflammatory cytokine that is linked to erythropoiesis inhibition and may contribute to anemia. However, the mechanism of IFN-γ-inhibited erythropoiesis is unknown. Activin A, a member of the transforming growth factor (TGF)-β superfamily, induces the erythropoiesis of hematopoietic progenitor cells. In this study, a luci...
Chronic myeloid leukemia (CML) is a hematopoietic stem/progenitor cell disorder in which Bcr-Abl oncoprotein inhibits cell differentiation. Differentiation induction is currently considered an alternative strategy for treating CML. Activin A, a member of the transforming growth factor-β superfamily, induces erythroid differentiation of CML cells th...
The polymerization of tubulin molecules forms microtubules which are considered an attractive target for cancer treatment. Herein, we synthesized a new tubulin inhibitor, MPT0B169 (2-dimethylamino-N-[1-(4-methoxy-benzenesulfonyl)-2, 3-dihydro-1H-indol-7-yl]-acetamide) and demonstrated its action in leukemia cell lines HL60 and NB4 and lymphoma cell...
The Notch pathway plays a role in the processes of cell proliferation, differentiation, and apoptosis, which affect the development and function of various organs. Dendritic cells (DCs), as professional antigen-presenting cells (APCs), induce T cell activation and promote T cell differentiation by antigen stimulation. Research has shown that Notch...
Preventive effects of Dll4-modulated dendritic cells on ovalbumin-induced asthmatic mice. (A) Brief protocol of animal sensitization and challenge. (B) Immunoglobulin E (IgE) and IgG2a anti-ovalbumin (OVA) antibody expression from OVA-immunized mice were measured by ELISA. (C) One day after the final OVA challenge, airway resistance was measured us...
Expression of oncogenic Bcr-Abl inhibits cell differentiation of hematopoietic stem/progenitor cells in chronic myeloid leukemia (CML). Differentiation therapy is considered to be a new strategy for treating this type of leukemia. Aclacinomycin A (ACM) is an antitumor antibiotic. Previous studies have shown that ACM induced erythroid differentiatio...
Type II collagen is known to modulate chondrogenesis of mesenchymal stem cells (MSCs). In this study, MSCs from human bone marrow aspirates were used to study the modulating effects of type II collagen on MSC differentiation during the early stages of osteogenesis and adipogenesis. With osteogenic induction, MSCs cultured on the type II collagen-co...
Cancer and inflammation related anemia is mediated by proinflammatory cytokines. However, the molecular mechanism of this cytokines‐inhibited erythropoiesis remains unclear. This study shows that proinflammatory cytokines, TNF‐α and IFN‐γ, inhibit activin A‐activated ζ‐globin promoter, but not IL‐1α, IL‐10 and IL‐13 in hematopoieticprogenitor cell...
In this study, phorbol-12-myristate-13-acetate (PMA) at low concentrations (<10 nM; L-PMA) induces the differentiation of CD14(+) monocytes into monocyte-derived macrophages (MDMs) while PMA at high concentrations (>100 nM; H-PMA) causes the apoptosis of these cells. The pre-treatment with Go6976 (a PKC-α/β(1) selective inhibitor), not anilinemonoi...
Activin A is a member of the transforming growth factor (TGF)-beta superfamily that regulates cell proliferation and differentiation. Using the p38 inhibitor SB203580, our previous studies demonstrated that p38 was involved in activin A-mediated hemoglobin (Hb) synthesis in K562 cells. SB203580 is an inhibitor of p38alpha and p38beta isoforms. In t...
Interferon alpha (IFN-alpha) modulates the proliferation of different human tumour cell lines. It has been shown that IFN-alpha induces the growth inhibition of T-cell acute lymphoblastic leukaemia (T-ALL). However, its intracellular signalling mechanisms remain unknown. This study found that IFN-alpha inhibited the cell proliferation of human T-AL...
Interleukin-5 (IL-5) induction of c-Myc expression is associated with IL-5 inhibition of apoptosis in hematopoietic cells. In this study, TFalpha1 and TFalpha8 cells with stable overexpression of IL-5 receptor alpha (IL-5Ralpha) subunit in TF-1 cells, a human hematopoietic progenitor cell line which expressed low levels of IL-5Ralpha, were used to...
The constitutively active Bcr-Abl tyrosine kinase plays a crucial role in chronic myelogenous leukemia (CML) pathogenesis. The Bcr-Abl protein induces the upregulation of proto-oncogene c-Jun, which is involved in Bcr-Abl transforming activity in Bcr-Abl positive cells. Recent studies reported that c-Jun inhibited hemoglobin synthesis in human CML...
The p38 mitogen-activated protein kinase (p38) is involved in multiple cellular functions such as cell proliferation and differentiation. Previously, we found that activin A mediated hemoglobin synthesis and cell growth inhibition through p38, whereas, basic fibroblast growth factor (bFGF) inactivated p38 to antagonize the activin A effects. In thi...
Eosinophils are important effector cells in the pathogenesis of allergic bronchial asthma. Enhancement of eosinophil apoptosis has been considered to have therapeutic effect on allergic disease. Fungal immunomodulatory peptide (FIP)-fve has been reported to possess immunoprophylactic activities for allergic diseases. The purpose of this study was t...
The human interleukin-3 receptor (hIL-3R) consists of a unique alpha subunit (hIL-3Ralpha) and a common beta subunit (betac). Binding of IL-3 to IL-3R activates Janus kinases JAK1 and JAK2. Our previously study showed that JAK2 and JAK1 were constitutively associated with the hIL-3Ralpha and betac subunits, respectively. In this study, we further d...
Activin A, a member of the transforming growth factor (TGF)-beta superfamily, is involved in the regulation of erythroid differentiation. Previous studies have shown that activin A inhibited the colony-forming activity of mouse Friend erythroleukemia cells, however, the mechanism remains unknown. First, we show herein that activin A induced the exp...
Epidermal growth factor (EGF) and endothelin-1 (ET-1) have been shown to be involved in proliferation and autoregeneration of renal tubular cells. This study aims to investigate the regulatory mechanism of ET-1-mediated EGF receptor (EGFR) transactivation in rat renal tubular cells (NRK-52E). Exposure of NRK-52E cells to ET-1 was found to stimulate...
JAK1 and JAK2 are tyrosine kinases involved in the regulation of cell proliferation, differentiation, and survival. These proteins may play a key role in mediating the effects of the cytokine IL-3 on hematopoietic cells. IL-3 induces tyrosine phosphorylation of both JAK1 and JAK2. However, it is not clear whether the activation of JAK1, JAK2, or bo...
Resveratrol-mediated heme oxgenase-1 (HO-1) induction has been shown to occur in primary neuronal cultures and has been implicated as having potential neuroprotective action. Further, antioxidant properties of resveratrol have been reported to protect against coronary heart disease. We attempted to examine the HO-1 inducing potency of resveratrol a...
Interleukin 5 (IL-5) inhibition of apoptosis is required throughout many hematopoietic lineages to regulate proliferation and differentiation. It is not clear how IL-5 mediates the intracellular molecular events regulating the anti-apoptotic effect. The cell lines TF-1 and JYTF-1 expressed different amounts of the IL-5 receptor alpha (IL-5R alpha)...
Activin A can induce erythroid differentiation, whereas basic fibroblast growth factor (bFGF) can maintain the undifferentiated status of erythroid progenitors. How these two factors together can affect the regulation of erythroid differentiation in hematopoietic cells has not been elucidated. This study demonstrates that bFGF antagonizes activin A...
Stem cell factor (SCF) has been suggested as essential for optimal production of various hematopoietic lineages mainly because of its apoptosis prevention function when it costimulates with other cytokines. However, the underlying mechanism of this synergism of apoptosis prevention is largely unknown. The present study examined the expression of so...
Stem cell factor (SCF) has been suggested as essential for optimal production of various hematopoietic lineages mainly because of its apoptosis prevention function when it costimulates with other cytokines. However, the underlying mechanism of this synergism of apoptosis prevention is largely unknown. The present study examined the expression of so...
Growth factors and cytokines play an important role in supporting cellular viability of various tissues during development due to their ability to suppress the default cell death program in each cell type. To date, neither the triggering molecule nor the transduction pathway of these default apoptosis programs is understood. In this study, we explo...
In vitro proliferation of hematopoietic stem cells requires costimulation by multiple regulatory factors whereas expansion of lineage-committed progenitor cells generated by stem cells usually requires only a single factor. The distinct requirement of factors for proliferation coincides with the differential temporal expression of the subunits of c...
In vitro proliferation of hematopoietic stem cells requires costimulation by multiple regulatory factors whereas expansion of lineage-committed progenitor cells generated by stem cells usually requires only a single factor. The distinct requirement of factors for proliferation coincides with the differential temporal expression of the subunits of c...
mcl-1, a bcl-2 family member, was originally identified as an early gene induced during differentiation of ML-1 myeloid leukemia cells.
In the present study, we demonstrate that Mcl-1 is tightly regulated by the granulocyte-macrophage colony-stimulating factor
(GM-CSF) signaling pathway. Upon deprivation of survival factor from TF-1 myeloid progeni...
In responding to the challenge of exogenous antigen(s), there is always a dramatic expansion of certain white blood cell populations in order to achieve tasks of self-defense. It is the cytokines secreted by various immunological cells which are responsible for provoking exponential proliferation and differentiation of these blood cells through bin...
