Ming-Jen Hsu

Taipei Medical University | TMU · Department of Pharmacology

Background Gemcitabine (GEM) faces challenges of poor oral bioavailability and extensive first-pass metabolism. Currently, only injectable formulations are available for clinical use. Hence, there is an urgent demand for the development of advanced, efficacious, and user-friendly dosage forms to maintain its status as the primary treatment for panc...

Increased medical attention is needed as the prevalence of autism spectrum disorder (ASD) rises. Both cardiovascular disorder (CVD) and hyperlipidemia are closely associated with adult ASD. Shank3 plays a key genetic role in ASD. We hypothesized that Shank3 contributes to CVD development in young adults with ASD. In this study, we investigated whet...

Albumin nanoparticles (NPs) and PEGylated liposomes have garnered tremendous interest as therapeutic drug carriers due to their unique physicochemical properties. These unique properties also have significant effects on the composition and structure of the protein corona formed around these NPs in a biological environment. Herein, protein corona fo...

Colorectal cancer is one of the most prevalent and lethal malignancies, affecting approximately 900,000 individuals each year worldwide. Patients with colorectal cancer are found with elevated serum interleukin-6 (IL-6), which is associated with advanced tumor grades and is related to their poor survival outcomes. Although IL-6 is recognized as a p...

Natural naphthoquinones and their derivatives exhibit a broad spectrum of pharmacological activities and have thus attracted much attention in modern drug discovery. However, it remains unclear whether naphthoquinones are potential drug candidates for anti-angiogenic agents. The aim of this study was to evaluate the anti-angiogenic properties of a...

Background and Purpose Benzimidazoles have attracted much attention over the last few decades due to their broad-spectrum pharmacological properties. Increasing evidence is showing the potential use of benzimidazoles as anti-angiogenic agents, although the mechanisms that impact angiogenesis remain to be fully defined. In this study, we aim to inve...

There is increasing evidence that statins, which are widely used in lowering serum cholesterol and the incidence of cardiovascular diseases, also exhibits anti‐tumour properties. The underlying mechanisms by which statins‐induced cancer cell death, however, remain incompletely understood. In this study, we explored the anti‐tumour mechanisms of a l...

Background and purpose: Angiogenesis and lymphangiogenesis are major routes for metastatic spread of tumor cells. It thus represent the rational targets for therapeutic intervention of cancer. Recently, we showed that a novel aliphatic hydroxamate-based compound, WMJ-S-001, exhibits anti-angiogenic, anti-inflammatory and anti-tumor properties. Howe...

Background and Purpose Recent development in drug discovery have shown benzimidazole to be an important pharmacophore,. Benzimidazole derivatives exhibit broad‐spectrum pharmacological properties including anti‐microbial, anti‐diabetic and anti‐tumour activity. However, whether benzimidazole derivatives are effective in suppressing angiogenesis and...

Growing evidence shows that hydroxamate-based compounds exhibit broad-spectrum pharmacological properties including anti-tumor activity. However, the precise mechanisms underlying hydroxamate derivative-induced cancer cell death remain incomplete understood. In this study, we explored the anti-tumor mechanisms of a novel aliphatic hydroxamate-based...

Background: The difficulties in breast cancer treatment are attributable to highly metastatic ability of breast cancer cells. The aberrant activation of epithelial-to-mesenchymal transition (EMT) contributes and enhances tumor metastasis. Growing evidence demonstrates that serum interleukin-6 (IL-6) level increases with tumor grade of breast cancer...

Background: Growing evidence shows that hydroxamate-based compounds exhibit broad-spectrum pharmacological properties including anti-tumor activity. It thus attracts much attention in the field of drug discovery. However, the precise mechanisms underlying hydroxamate derivatives' anti-tumor actions remains incomplete understood. Methods: In this st...

Background: Accumulation of amyloid-beta peptide (Abeta) in senile plaques in the brain has been implicated in the pathogenesis of Alzheimer's disease (AD). Abeta also deposits in brain blood vessels, leading to the development of cerebral amyloid angiopathy (CAA). CAA increased vulnerability to hemorrhagic and ischemic strokes in the elderly. The...

CME-1, a novel water-soluble polysaccharide purified from Ophiocordyceps sinensis mycelia, has anti-oxidative, antithrombotic and antitumour properties. In this study, other major attributes of CME-1, namely anti-inflammatory and immunomodulatory properties, were investigated. Treating lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with CME-1...

Abnormal proliferation of vascular smooth muscle cells (VSMCs) gives rise to major pathological processes involved in the development of cardiovascular diseases. The use of anti-proliferative agents for VSMCs offers potential for the treatment of vascular disorders. Intravenous anesthetics are firmly established to have direct effects on VSMCs, res...

Background and purpose: Histone deacetylase (HDAC) inhibitors with broad-spectrum anti-tumor properties has been described and attracted lots of attention in the field of drug discovery. However, the underlying anti-tumor mechanisms of HDAC inhibitors remain incompletely understood. In this study, we aimed to characterize the underlying mechanisms...

Some hydroxamate compounds induce cancer cell death by intracellular reactive oxygen species (ROS). This study introduced the hydroxamate core into lovastatin, a fungus metabolite clinically used for the treatment of hypercholesterolemia. The resulting compounds were evaluated for the activity for inducing ROS production. Most compounds exhibited h...

Elevated serum interleukin-6 (IL-6) levels correlates with tumor grade and poor prognosis in cancer patients. IL-6 has been shown to promote tumor lymphangiogenesis through vascular endothelial growth factor-C (VEGF-C) induction in tumor cells. We recently showed that IL-6 also induced VEGF-C expression in lymphatic endothelial cells (LECs). Howeve...

Transfection efficiency in SV-LECs. SV-LECs were transfected with control vector (pcDNA) or a green fluorescence protein expression vector pEGFP as described in the “Materials and methods” section. After transfection, cells were harvested and resuspended in PBS. Green fluorescence derived from successful transfected cells were determined by flow-cy...

Statins are used widely to lower serum cholesterol and the incidence of cardiovascular diseases. Growing evidence shows that statins also exhibit beneficial effects against cancers. In this study, we investigated the molecular mechanisms involved in lovastatin-induced cell death in Fadu hypopharyngeal carcinoma cells. Lovastatin caused cell cycle a...

Stroke pathogenesis involves complex oxidative stress-related pathways. The nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) pathways have been considered molecular targets in pharmacologic intervention for ischemic diseases. Andrographolide, a labdane diterpene, has received increasing attention in recent years becaus...

Hydroxamate derivatives have attracted considerable attention due to their broad pharmacological properties and have been extensively investigated. We recently demonstrated that WMJ-S-001, a novel aliphatic hydroxamate derivative, exhibits anti-inflammatory and anti-angiogenic activities. In this study, we explored the underlying mechanisms by whic...

The lymphatic endothelium plays an important role in the maintenance of tissue fluid homeostasis. It also participates in the pathogenesis of several inflammatory diseases. However, little is known about the underlying mechanisms by which lymphatic endothelial cell responds to inflammatory stimuli. In this study, we explored the mechanisms by which...

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is important in the pathogenesis of vascular disorders such as atherosclerosis and restenosis. Hinokitiol, a tropolone derivative found in Chamacyparis taiwanensis, has been found to exhibit anticancer activity in a variety of cancers through inhibition of cell proliferation. In the pre...

Hydroxamate derivatives have been attracted considerable attention, due to their broad pharmacological properties. Recent studies reported their potential use in the treatment of cardiovascular diseases, arthritis or infectious diseases. However, the inhibitory mechanisms of hydroxamate derivatives in inflammation remain to be elucidated. In an eff...

Angiogenesis, one of the major routes for tumor invasion and metastasis represents a rational target for therapeutic intervention. Recent development in drug discovery has highlighted the diverse biological and pharmacological properties of hydroxamate derivatives. In this study, we characterized the anti-angiogenic activities of a novel aliphatic...

The abnormal growth of vascular smooth muscle cells (VSMCs) is considered a critical pathogenic process in inflammatory vascular diseases. We have previously demonstrated that protein phosphatase 2 A (PP2A)-mediated NF-κB dephosphorylation contributes to the anti-inflammatory properties of andrographolide, a novel NF-κB inhibitor. In this study, we...

Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In t...

Figure S5 Effects of N-acetylcysteine (NAC) on p65 phosphorylation and dimethyl-PP2A (DM-PP2A) expression in LPS/IFN-γ-activated VSMCs.

The hydrophilic α-tocopherol derivative, 2,2,5,7,8-pentamethyl-6-hydroxychromane (PMC), is a promising alternative to vitamin E in clinical applications. Critical vascular inflammation leads to vascular dysfunction and vascular diseases, including atherosclerosis, hypertension and abdominal aortic aneurysms. In this study, we investigated the mecha...

Inflammation and vascular perturbations are increasingly implicated in the pathogenesis of neurodegenerative diseases. Prevailing evidence suggests that valproic acid (VPA), an antiepileptic and mood stabilizer, exhibits not only neuro-protective effects, but also anti-inflammatory effects in neurodegenerative diseases. However, the underlying mech...

Angiogenesis occurs during tissue growth, development and wound healing. It is also required for tumor progression and represents a rational target for therapeutic intervention. NBM-T-BMX-OS01 (BMX), derived from the semisynthesis of osthole, an active ingredient isolated from Chinese herb Cnidium monnieri (L.) Cuss., was recently shown to enhance...

Formation of lymphatic capillaries by lymphatic endothelial cells (LECs) occurs both in normal tissues as well as in pathological processes including tumor metastasis. Interleukin-6 (IL-6), a potent pro-inflammatory cytokine, has been shown to be highly elevated in various cancers. IL-6 has also been shown to increase tumor lymphangiogenesis throug...

Background: Statins, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors with cholesterol-lowering properties, were recently shown to exhibit anti-cancer effects. However, the molecular mechanism underlying statin-induced cancer cell death remains to be elucidated. Elevated level of survivin is often found over-expressed in human cancer...

Atherosclerosis is linked with the development of many cardiovascular complications. Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in the development of atherosclerosis. Accordingly, the apoptosis of VSMCs, which occurs in the progression of vascular proliferation, may provide a beneficial strategy for managing...

Denbinobin, a phenanthraquinone derivative, was shown to exert antitumor activities in several types of cancer cell lines. However, the precise mechanism underlying denbinobin-induced cell death remains unclear. In this study, we investigated the apoptotic signaling cascade elicited by denbinobin in human glioblastoma multiforme (GBM) cells. Denbin...

Thrombin might activate c-Src to induce JAK2 activation, which causes STAT3 activation, inducing CCN2 expression in human lung fibroblasts. Thrombin is a multifunctional serine protease and an important fibrotic mediator that induces CCN2 expression. We previously showed that thrombin induces CCN2 expression via an ASK1-dependent JNK/AP-1 pathway i...

Background Zerumbone, a sesquiterpene compound isolated from subtropical ginger, Zingiber zerumbet Smith, has been documented to exert antitumoral and anti- inflammatory activities. In this study, we demonstrate that zerumbone induces apoptosis in human glioblastoma multiforme (GBM8401) cells and investigate the apoptotic mechanism. Methods We add...

Andrographolide, a novel nuclear factor-κB (NF-κB) inhibitor, is isolated from leaves of Andrographis paniculata. Platelet activation is relevant to a variety of coronary heart diseases. Our recent studies revealed that andrographolide possesses potent antiplatelet activity by activating the endothelial nitric oxide synthase (eNOS)-NO-cyclic GMP pa...

To investigate the signaling pathways involved in thrombin-induced connective tissue growth factor (CTGF) expression in rat vascular smooth muscle cells (VSMCs). Experiments were preformed on primary rat aortic smooth muscle cells (RASMCs) and a rat VSMC line (A10). CTGF protein levels were measured using Western blotting. Luciferase reporter genes...

Elevated levels of survivin and histone deacetylases (HDACs) are often found over-expressed in human cancers, including colorectal cancer, and have been implicated in tumorigenesis. HDAC inhibition induces growth arrest and cell death in various transformed cell; however, the mechanisms by which this reduces cell viability in colorectal cancer cell...

Plasminogen activator inhibitor-1 (PAI-1), primarily up-regulated by transforming growth factor (TGF)-β, is essential in the development of fibrosis. Histone deacetylase (HDAC) was shown to modulate gene expression and fibrogenesis in various tissues. However, the implications of HDAC in terms of PAI-1 expression and pleural fibrosis remain unclear...

The lymphatic vasculature is involved in the transportation of tissue fluids, extravasated plasma proteins and cells back into blood circulation. Formation of lymphatic vessels by lymphatic endothelial cells (LECs) occurs both in normal tissues as well as in pathological processes including inflammation, lymphedema and tumor metastasis. Recent repo...

Histone deacetylase (HDAC) inhibitors have emerged as a new class of antitumor agents because they were demonstrated to induce cell cycle arrest, promote cell apoptosis, and inhibit metastasis. Recently, HDAC inhibitors were also shown to exhibit pronounced anti-inflammatory properties. However, the underlying mechanism contributing to the suppress...

Histone deacetylase (HDAC) inhibitors were demonstrated to induce cell cycle arrest, promote cell differentiation or apoptosis, and inhibit metastasis. HDAC inhibitors have thus emerged as a new class of anti-tumor agents for various types of tumors. However, the mechanisms by which HDAC inhibition-induced cell death remain to be fully defined. In...

Recent studies have demonstrated that transcription factor nuclear factor (NF)-κB inhibition may contribute to the protective anti-inflammatory actions of andrographolide, an abundant component of plants of the genus Andrographis. However, the precise mechanism by which andrographolide inhibits NF-κB signaling remains unclear. We thus investigated...

Recent studies demonstrated that transcription factor nuclear factor (NF)-κB inhibition may contribute to the protective anti-inflammatory actions of andrographolide, an abundant component of plants of the genus Andrographis. However, the precise mechanism by which andrographolide inhibits NF-κB signaling remains unclear. We thus investigated the m...

Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development of cardiovascular diseases. PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane) is the most potent hydrophilic derivative of vitamin E. In this study, we investigated the mechanisms of PMC inhibition of VSMC proliferation in vitro and in vivo. PMC (2...

Aberrant remodeling of the extracellular matrix occurs in many pathological processes, and its breakdown is mainly accomplished by matrix metalloproteinases (MMPs), which participate in the course of inflammation and tumor invasion. Nuclear factor-kappaB (NF-kappaB), a key transcription factor for the production of MMP-9, can be activated by variou...

Prevailing evidence suggests that amyloid beta peptide (Aβ), a key mediator in age-dependent neuronal and cerebrovascular degeneration, activates death signaling processes leading to neuronal as well as non-neuronal cell death in the central nervous system. A major cellular event in Aβ-induced death of non-neuronal cells, including cerebral endothe...

PGN activates TLR2-mediated PP2A-ASK1-JNK-AP-1-C/EBPβ cascade and subsequent COX-2 expression in macrophages. In this study, we investigated the role of ASK1 in PGN-induced C/EBPβ activation and COX-2 expression in RAW 264.7 macrophages. The PGN-induced COX-2 expression was attenuated by the DNs of ASK1, JNK1, JNK2, a JNK inhibitor (SP600125), and...

In this study, we examined the role of phosphatidylcholine-phospholipase C (PC-PLC) and protein kinase C (PKC) in peptidoglycan (PGN)-induced nuclear factor-kappaB (NF-kappaB) activation and cyclooxygenase-2 (COX-2) expression in RAW 264.7 macrophages. PGN-induced COX-2 expression was attenuated by a PC-PLC inhibitor (D609) and by PKC inhibitors (G...

Thrombin plays an important role in lung inflammatory diseases. Thrombin can induce connective tissue growth factor (CTGF) expression in lung fibroblasts. However, little is known about the signaling pathway in thrombin-induced CTGF expression. In this study, we investigated the role of apoptosis signal-regulating kinase 1 (ASK1) in thrombin-induce...

The sphingomyelin signal transduction pathway is known to play a role in mediating the action of various cytokines. Herein, we examined the role of neutral sphingomyelinase (nSMase)/ceramide in peptidoglycan (PGN)-induced NF-kappaB activation and cyclooxygenase-2 (COX-2) expression in macrophages. PGN-induced COX-2 expression was attenuated by an n...

In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1) in denbinobin-induced apoptosis in human lung adenocarcinoma (A549) cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN), two antioxidants (N-acetyl-L-cysteine (NAC) and glutathione (GSH)), a c-Jun N-terminal kina...

Previously, we found that peptidoglycan (PGN), a cell wall component of the gram-positive bacterium Staphylococcus aureus, may activate the Ras/Raf-1/extracellular signal-regulated kinase (ERK) pathway, which in turn initiates IκB kinases α/β (IKKα/β) and nuclear factor-κB (NF-κB) activation, and ultimately induces cyclooxygenase-2 (COX-2) expressi...

Increasing evidence demonstrated that denbinobin, isolated from Ephemerantha lonchophylla, exert cytotoxic effects in cancer cells. The purpose of this study was to investigate whether denbinobin induces apoptosis and the apoptotic mechanism of denbinobin in human lung adenocarcinoma cells (A549). Denbinobin (1-20microM) caused cell death in a conc...

A pathological hallmark of Alzheimer's disease is accumulation of amyloid-beta peptide (Abeta) in senile plaques. Abeta has also been implicated in vascular degeneration in cerebral amyloid angiopathy because of its cytotoxic effects on non-neuronal cells, including cerebral endothelial cells (CECs). We explore the role of apoptosis signal-regulati...

A previous report showed that transforming growth factor-beta1 (TGF-beta1) can induce heme oxygenase-1 (HO-1) expression, attenuate cellular injury, and maintain tissue homeostasis. In this study, we investigated the involvement of phosphoinositide-3-OH-kinase (PI3K)/Akt and the nuclear factor-kappaB (NF-kappaB) signaling pathway in TGF-beta1-induc...

In this study, we examined the regulation of NF-κB activation and IL-8/CXCL8 expression by thrombin in human lung epithelial cells (EC). Thrombin caused a concentration-dependent increase in IL-8/CXCL8 release in a human lung EC line (A549) and primary normal human bronchial EC. In A549 cells, thrombin, SFLLRN-NH 2 (a protease-activated receptor 1...

In this study, we investigated the signaling pathway involved in IL-6 production caused by peptidoglycan (PGN), a cell wall component of the Gram-positive bacterium, Staphylococcus aureus, in RAW 264.7 macrophages. PGN caused concentration- and time-dependent increases in IL-6, PGE(2), and cAMP production. PGN-mediated IL-6 production was inhibited...