Phuong Thien Thuong

National Institute of Medicinal Materials, Hà Nội, Ha Nội, Vietnam

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Publications (66)125.25 Total impact

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    Full-text · Article · Dec 2015 · Asia-Pacific Journal of Clinical Oncology
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    ABSTRACT: Glucose uptake into insulin-sensitive tissues is important for the regulation of blood glucose. This study has investigated whether the pentacyclic triterpenoids substituted with a carboxylic acid at the C-27 position isolated from Astilbe rivularis can enhance glucose uptake and subsequently to also examine their underlying molecular mechanisms. The structure of the new pentacyclic triterpenoid 1 was assigned by spectroscopic data interpretation. To evaluate the activity of compounds 1 and 2, glucose uptake and glucose transporter 4 (GLUT4) translocation were measured in C2C12 myotubes. The C-27-carboxylated triterpenoids 1 and 2 significantly increased basal and insulin-stimulated glucose uptake and GLUT4 translocation to plasma membrane. Both compounds stimulated the phosphorylation of insulin receptor substrate-1 (IRS-1), protein kinase B (Akt), and extracellular signal-regulated kinase 1/2 (Erk1/2). Pretreatment with the Akt inhibitor triciribine or the Erk1/2 inhibitor U0126 decreased the ability of both compounds to enhance basal- and insulin-stimulated glucose uptake and stimulate GLUT4 translocation. These results indicate that compounds 1 and 2 activated both the IRS-1/Akt and Erk1/2 pathways and subsequently stimulated GLUT4 translocation, leading to enhanced glucose uptake. Thus, these observations suggest that C-27-carboxylated-pentacyclic triterpenoids may serve as scaffolds for development as agents for the management of blood glucose levels in disease states such as diabetes.
    Full-text · Article · Apr 2015 · Journal of Natural Products
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    ABSTRACT: To search for new chemotherapeutic agents to treat colorectal cancer, we isolated a number of natural ent-kaurane diterpenoids from the plant Croton tonkinensis. Among them, only CeKDs with the 15-oxo-16-ene moiety induced the apoptosis of colorectal cancer cell lines Caco-2 and LS180. The active CeKD induced the activation of ERK and JNK, but the inactive ones induced that of ERK, but not that of JNK. It thus appears that JNK seemed to play an important role in the apoptotic activity of the active compounds. The dual-specificity JNK kinase MKK4 was activated in both colorectal cancer cells treated with the active CeKD, but MKK7 was not activated. Further, the active CeKD, but not the inactive one, enhanced the generation of intracellular reactive oxygen species (ROS) in both cells. CeKD-induced cell apoptosis and ROS generation, as well as JNK activation, were inhibited by the antioxidant N-acetyl-L-cysteine. These findings suggest that ROS stimulated the phosphorylation of JNK mediated by MKK4 and played a critical role in CeKD-induced apoptosis in colorectal cancer cells.
    No preview · Article · Jan 2014 · Anti-cancer agents in medicinal chemistry
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    ABSTRACT: Four lignans, meso-dihydroguaiaretic acid (DHGA), macelignan, fragransin A2 and nectandrin B, were isolated from the seeds of Myristica fragrans (Vietnamese nutmeg) and investigated for their cytotoxic activity against eight cancer cell lines. Of these, DHGA exhibited potent cytotoxicity against H358 with IC50 value of 10.1 μM. In addition, DHGA showed antitumor activity in allogeneic tumor-bearing mice model.
    Full-text · Article · Jul 2013 · Archives of Pharmacal Research
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    ABSTRACT: Pristimerin is a naturally occurring triterpenoid that causes cytotoxicity in several cancer cell lines. However, the mechanism of action for the cytotoxic effect of pristimerin has not been unexplored. The purpose of this study was to investigate the effect of pristimerin on cytotoxicity using the epidermal growth factor receptor 2 (HER2)-positive SKBR3 human breast cancer cell line. Pristimerin inhibited proliferation in dose- and time-dependent manners in cells. We found it to be effective for suppressing HER2 protein and mRNA expression. Fatty acid synthase (FASN) expression and FASN activity were downregulated by pristimerin. Adding of exogenous palmitate, the end product of de novo fatty acid synthesis, reduced the proliferation activity of pristimerin. The changes in HER2 and FASN expression induced by pristimerin altered the levels of Akt and mitogen-activated protein kinase (MAPK) phosphorylation (Erk1/2, p38, and c-Jun N-terminal kinase (JNK)). Pristimerin lowered the levels of phosphorylated mammalian target of rapamycin (mTOR) and its downstream targets such as phosphoprotein 70 ribosomal protein S6 kinase and 4E binding protein1. Pristimerin inhibited migration and invasion of cells, and co-treatment with the mTOR inhibitor rapamycin additionally suppressed these activities. Pristimerin-induced apoptosis was evaluated using Western blotting for caspase-3, -8, -9, and poly (ADP-ribose) polymerase expression and flow cytometric analysis for propidium iodide labeling. These results suggest that pristimerin is a novel HER2-downregulated compound that is able to decrease fatty acid synthase and modulate the Akt, MAPK, and mTOR signaling pathways to influence metastasis and apoptosis. Pristimerin may be further evaluated as a chemotherapeutic agent for HER2-positive breast cancers.
    No preview · Article · Feb 2013 · Biological & Pharmaceutical Bulletin
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    ABSTRACT: Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high mortality worldwide. Traditional chemotherapy for HCC is not widely accepted by clinical practitioners because of its toxic side effects. Thus, there is a need to identify chemotherapeutic drugs against HCC. AMP-activated protein kinase (AMPK) is a biologic sensor for cellular energy status that acts a tumor suppressor and a potential cancer therapeutic target. The traditional Vietnamese medicinal plant Croton tonkinensis shows cytotoxicity in various cancer cells; however, its anticancer mechanism remains unclear. In this study, we determined whether the ent-kaurane diterpenoid ent-18-acetoxy-7β-hydroxy kaur-15-oxo-16-ene (CrT1) isolated from this plant plays a role as a chemotherapeutic drug targeting AMPK. CrT1 blocked proliferation in dose- and time-dependent manners in human hepatocellular carcinoma SK-HEP1 cells. CrT1 induced sub-G(1) arrest and caspase-dependent apoptosis. CrT1 activated caspase-3, -7, -8, -9, and poly(ADP-ribose) polymerase, and its effect was inhibited by z-VAD-fmk suppressing caspase-3 cleavage. CrT1 induced increases in p53 and Bax levels but decreased Bcl(2) levels. In addition, CrT1 resulted in increased translocation of cytochrome c into the cytoplasm. We showed that CrT1-activated AMPK activation was followed by modulating the mammalian target of rapamycin/p70S6K pathway and was inactivated by treating cells with compound C. Treatment with CrT1 and aminoimidazole carboxamide ribonucleotide (AICAR) synergistically activated AMPK. CrT1-induced AMPK activation regulated cell viability and apoptosis. These results suggest that CrT1 is a novel AMPK activator and that AMPK activation in SK-HEP1 cells is responsible for CrT1-induced anticancer activity including apoptosis.
    No preview · Article · Jan 2013 · Biological & Pharmaceutical Bulletin
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    ABSTRACT: Highlights ► A new saponin and nine known compounds were isolated from Anemone rivularis. ► Structures were elucidated on the basis of spectroscopic analysis. ► New saponin can be utilized as a chemical marker for the taxonomy of A. rivularis.
    No preview · Article · Oct 2012 · Biochemical Systematics and Ecology
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    ABSTRACT: The emergence of the H1N1 swine flu pandemic has the possibility to develop the occurrence of disaster- or drug-resistant viruses by additional reassortments in novel influenza A virus. In the course of an anti-influenza screening program for natural products, 10 xanthone derivatives (1-10) were isolated by bioassay-guided fractionation from the EtOAc-soluble extract of Polygala karensium. Compounds 1, 3, 5, 7, and 9 with a hydroxy group at C-1 showed strong inhibitory effects on neuraminidases from various influenza viral strains, H1N1, H9N2, novel H1N1 (WT), and oseltamivir-resistant novel H1N1 (H274Y) expressed in 293T cells. In addition, these compounds reduced the cytopathic effect of H1N1 swine influenza virus in MDCK cells. Our results suggest that xanthones from P. karensium may be useful in the prevention and treatment of disease by influenza viruses.
    No preview · Article · Apr 2012 · Bioorganic & medicinal chemistry letters
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    ABSTRACT: AMP-activated protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes. Recent studies indicate that AMPK activation strongly suppresses cell proliferation in tumor cells, which requires high rates of protein synthesis and de novo fatty acid synthesis for their rapid growth. Pomolic acid (PA) has been previously described as being active in inhibiting the growth of cancer cells. In this study, we investigated PA activated AMPK, and this activity was related to proliferation and apoptosis in MCF7 breast cancer cells. PA inhibited cell proliferation and induced sub-G(1) arrest, elevating the mRNA levels of the apoptotic genes p53 and p21. PA activated caspase-3, -9, and poly(ADP-ribose) polymerase, and this effect was inhibited by z-VAD-fmk. AMPK activation was increased by treating cells with PA, inactivated by treating cells with a compound C, and co-treatment consisting of PA and aminoimidazole carboxamide ribonucleotide (AICAR) synergistically activated AMPK. These anti-cancer potentials of PA were accompanied by effects on de novo fatty acid synthesis as shown by the decreased expression of fatty acid synthase, and decreased acetyl-CoA carboxylase activation and incorporation of [(3)H]acetyl-CoA into fatty acids. In addition, PA inhibited key enzymes involved in protein synthesis such as mammalian target of rapamycin (mTOR), 70 kDa ribosomal protein S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). These results suggest that PA exerts anti-cancer properties through the modulation of AMPK pathways and its value as an anti-cancer agent in breast cancer therapy.
    No preview · Article · Jan 2012 · Biological & Pharmaceutical Bulletin
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    ABSTRACT: Breast cancer is the most common malignant tumor in women these days accounting for approximately 24% of all cancer. During our screening program searching for cytotoxic materials from natural products, two new symmetric dimers of ent-kaurane diterpenoid, crotonkinensins C (1) and D (2), with connectivity at C-17 were isolated from the leaves of the Vietnamese endemic medicinal plant Croton tonkinensis. Their structures were determined on the basis of physicochemical and spectroscopic data. Compound 2 showed a potent cytotoxic activity against MCF-7, tamoxifen-resistant MCF-7 (MCF-7/TAMR), adriamycin-resistant MCF-7 (MCF-7/ADR), and MDA-MB-231 breast cancer cell lines.
    No preview · Article · Dec 2011 · Bioorganic & medicinal chemistry letters
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    ABSTRACT: Several isoquinoline alkaloids (1-18), which have basic chemical structures as protoberberine and aporphine skeletones, were evaluated for their inhibitory activities on AChE and BuChE. Among them, compounds 3, 4, 6, 8 and 12 showed the potent AchE activity with the IC50 values ranging from 10.2 ± 0.5 μM to 24.5 ± 1.6 μM, meanwhile, compound 14-17 exhibited strong inhibitory activity with IC50 values from 2.1 ± 0.2 to 5.5 ± 0.3 μM. Compounds 14-17 exhibited selective inhibition for AChE compared with BuChE. The isoquinoline alkaloid possesses aromatic methylenedioxy groups and quaternary nitrogen atoms are crucial for the anti-cholinesterase inhibitory activity.
    Full-text · Article · Jun 2011 · Natural Product Sciences
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    ABSTRACT: Phytochemical study on the ethanol extract of a Crinum species by bioassay-guided fractionation resulted in the isolation of an active principle, which was determined as parthenin (1) on the basis of physicochemical and spectroscopic analyses. This is the first report on the existence of a sesquiterpenoid from Crinum ensifolium. Compound 1 was found to show strong cytotoxic activity against some cancer cell lines and strongly inhibit NF-κB activity with the IC50 value of 1.82 μM.
    No preview · Article · Jun 2011 · Natural Product Sciences
  • M. Na · P.T. Thuong · K.H. Bae
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    ABSTRACT: Reactive oxygen species potentially cause damage to cellular components including lipids, protein and DNA; this oxidative damage plays a key role in the pathogenesis of neurodegenerative disease, cardiovascular disease, metabolic disease and cancer. On the basis of the oxidative stress hypothesis, a number of studies have been performed to search for an efficient and safe antioxidant. Although in vitro studies have provided promising results, only a limited number of natural and synthetic antioxidants have been developed for clinical application due to their low efficacy and side-effects. Thus, the discovery of new antioxidants with marked efficacy and safety has attracted worldwide attention in recent decades. Since plants are recognized as important sources of natural antioxidants, our research has focused on the discovery of new naturally occurring antioxidants from medicinal plants. The purpose of this review is to open a new prospect in the field of search for natural antioxidants from medicinal plants by summarizing our recent findings. Using in vitro bioassay systems such as 2,2-diphenyl-1- picrylhydrazyl, superoxide radical scavenging tests and lipid peroxidation models, we have tested over than 350 species of medicinal plants for their antioxidant activity and selected several of them for further investigation. During the research on the discovery of effective natural antioxidants from the medicinal plants selected, we have isolated several new and known antioxidant compounds that include stilbene glycosides, phenolic glycosides, flavonoids, oligostilbenes, and coumarins. Our results suggest that the presence of antioxidant compounds in the medicinal plants might be associated with the traditional use to treat inflammation, cardiovascular disease and various chronic diseases.
    No preview · Article · Jun 2011 · Natural Product Sciences
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    Young Ju Bae · Phuong Thien Thuong · Nacksung Kim · Won Keun Oh · Jin Hee Kim · Junwon Lee
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    ABSTRACT: Osteoclasts play an important role in bone metabolism by resorbing the bone matrix. Thus, the compounds inhibiting osteoclasts can treat bone diseases such as osteoporosis. Among the 8 triterpenoids tested, we show that Ilekudinol B isolated from the plant Weigela subsessilis inhibits receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis from bone marrow-derived monocyte/macrophage cells in a dose-dependent manner, whereas it has no significant effect on osteoblast differentiation. Furthermore, Ilekudinol B attenuates the induction of nuclear factor of activated T cells (NFAT) c1 and osteoclast-associated receptor (OSCAR) expression. Our results indicate that Ilekudinol B has the potential to inhibit osteoclast formation by attenuating the signaling cascades associated with RANKL.
    Preview · Article · Apr 2011 · Journal of medicinal plant research
  • Nguyen Hai Nam · Phan Thi Phuong Dung · Phuong Thien Thuong
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    ABSTRACT: A series of 2-phenylbenzothiazoles has been synthesized either by i) condensation of different aromatic aldehydes with 2-aminothiophenol or ii) condensation of N-(2-chlorophenyl)benzothioamides in KOH catalyzed by potassium fericyanide. The structures of synthesized compounds were confirmed by IR, MS, and (1)H-NMR. The results of biological activity screening showed that six compounds including 2-phenylbenzothiazol (1a), 2-(2-chlorophenyl)benzothiazole (1b), 2-(3-chlorophenyl)benzothiazole (1c), 2-(4-hydroxyphenyl)benzothiazole (1e), 2-(4-dimethylaminophenyl)benzothiazole (1h) and 2-(2,3,4-trimethoxyphenyl)benzothiazole (1i) exhibited significant antibacterial activities; two compounds (1a, 1e) exhibited antifungal activities. Especially, 1e showed considerable antimicrobial activity against both A. niger and F. oxysporum. The brominated derivative of 1e displayed extended spectrum against all four bacterial strains tested with lower MIC values. In vitro cytotoxicity of the synthesized compounds was evaluated on three cancer cell lines (A549, HT1080, MCF7-MDR). The results indicated that three compounds (1e, 1g, 1i) exhibited significant cytotoxic activity on A549 and MCF7-ADR cells (IC(50), 10.07-13.21 μg/ml). Brominated and nitrated derivatives (1k, 1l, respectively) of 1e exhibited even more potent cytotoxicity.
    No preview · Article · Mar 2011 · Medicinal chemistry (Shāriqah (United Arab Emirates))
  • Nguyen Hai Nam · Phan Thi Phuong Dung · Phuong Thien Thuong
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    ABSTRACT: A series of 2-phenylbenzothiazoles has been synthesized either by i) condensation of different aromatic aldehydes with 2-aminothiophenol or ii) condensation of N-(2-chlorophenyl)benzothioamides in KOH catalyzed by potassium fericyanide. The structures of synthesized compounds were confirmed by IR, MS, and 1H-NMR. The results of biological activity screening showed that six compounds including 2-phenylbenzothiazol (1a), 2-(2-chlorophenyl)benzothiazole (1b), 2- (3-chlorophenyl)benzothiazole (1c), 2-(4-hydroxyphenyl)benzothiazole (1e), 2-(4-dimethylaminophenyl)benzothiazole (1h) and 2-(2,3,4-trimethoxyphenyl)benzothiazole (1i) exhibited significant antibacterial activities; two compounds (1a, 1e) exhibited antifungal activities. Especially, 1e showed considerable antimicrobial activity against both A. niger and F. oxysporum. The brominated derivative of 1e displayed extended spectrum against all four bacterial strains tested with lower MIC values. In vitro cytotoxicity of the synthesized compounds was evaluated on three cancer cell lines (A549, HT1080, MCF7-MDR). The results indicated that three compounds (1e, 1g, 1i) exhibited significant cytotoxic activity on A549 and MCF7-ADR cells (IC50, 10.07-13.21μg/ml). Brominated and nitrated derivatives (1k, 1l, respectively) of 1e exhibited even more potent cytotoxicity.
    No preview · Article · Feb 2011 · Medicinal Chemistry
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    ABSTRACT: Corosolic acid is one of the triterpenoids present in the leaves of Weigela subsessilis. The antidiabetic activity of corosolic acid has been reported previously, but to date, the anticancer effects on gastric cancer have been poorly studied. In this study, corosolic acid showed growth inhibition on SNU-601 human gastric cancer cells, with an IC₅₀ value of 16.9 ± 2.9 μM. Corosolic acid also triggered the activation of caspase-3 and poly (ADP-ribose) polymerase, while it was recovered by Z-VAD-FMK. Moreover, the cell growth/apoptosis activities of corosolic acid were regulated by the AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signals. These results showed that corosolic acid-mediated AMPK activation leads to inhibition of mTOR, thus providing a possible mechanism of action of corosolic acid in the inhibition of cancer cell growth and the induction of apoptosis.
    No preview · Article · Dec 2010 · Phytotherapy Research
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    ABSTRACT: During the screening effort to discover new types of protein tyrosine phosphatase 1B (PTP1B) inhibitors, it was found that a MeOH extract of the leaves and stems of Weigela subsessilis (Caprifoliaceae) inhibited the enzyme activity. By means of an in vitro bioassay-guided fractionation on the MeOH extract, two 24-norursane triterpenes, ilekudinol A (1) and ilekudinol B (2), were isolated as active metabolites. Compounds 1 and 2 inhibited PTP1B with IC(50) values of 29.1 ± 2.8 and 5.3 ± 0.5 μM, respectively. Kinetic studies suggest that both 1 and 2 are non-competitive inhibitors of PTP1B. The findings indicate that the free carboxyl group at C-28 in this type of triterpenes plays a critical role in the inhibition of PTP1B.
    No preview · Article · Nov 2010 · Phytotherapy Research
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    ABSTRACT: Overexpression/amplification of human epidermal growth factor receptor (HER)2/neu (erbB-2) oncogene plays a causal role in carcinogenesis and correlates with a poor clinical prognosis. However, little is known about HER2 in gastric cancer. In this study, we explored the pharmacological activities of natural triterpenoid corosolic acid (CRA) in HER2 signaling and its role in gastric cancer development and progression. In this study, CRA dramatically inhibited HER2 expression in a dose- and time-dependent manner, effectively inhibited cell proliferation, and induced G(0)/G(1) arrest through the induction of p27(kip1) and cyclin D(1) down-regulation. CRA exposure enhanced apoptotic cell death, as confirmed by caspase-3 and poly (ADP-ribose) polymerase cleavage activities. CRA inhibited signaling pathways downstream of HER2, including phospho-proteins such as Akt and Erk. In addition, CRA combined with adriamycin and 5-fluorouracil enhanced this growth inhibition, but not with docetaxel and paclitaxel. These findings demonstrate that CRA suppresses HER2 expression, which in turn promotes cell cycle arrest and apoptotic cell death of gastric cancer cells, providing a rationale for future clinical trials of CRA in the treatment of HER2-positive gastric cancers.
    No preview · Article · Jun 2010 · Biological & Pharmaceutical Bulletin
  • Nguyen Hai Nam · Phan Thi Phuong Dung · Phuong Thien Thuong · Tran Thi Hien
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    ABSTRACT: A series of benzothiazole derivatives including N-(benzo[d]thiazol-2-yl)cyclohexanecarboxamides (2a-g) and N-(benzo[d]thiazol-2-yl)cyclohexancarbothioamides (3b-d) have been synthesized and evaluated for cytotoxic and antimicrobial activities. Two compounds including N-(6-ethoxybenzo[d]thiazol-2-yl)cyclohexanecarboxamide (2c) and N-(6-ethoxybenzo[d]thiazol-2-yl)cyclohexanecarbothiamide (3c) demonstrated significant cytotoxicity against three cancer cell lines (A549, MCF7-MDR and HT1080) while most of compounds exhibited moderate inhibitory effects on the growth of Staphyllococcus aureus and some other fungi.
    No preview · Article · May 2010 · Medicinal chemistry (Shāriqah (United Arab Emirates))

Publication Stats

939 Citations
125.25 Total Impact Points

Institutions

  • 2009-2015
    • National Institute of Medicinal Materials
      Hà Nội, Ha Nội, Vietnam
    • University of Yaoundé II
      Jaúnde, Centre Region, Cameroon
  • 2010-2013
    • Vietnam National University, Hanoi
      Hà Nội, Ha Nội, Vietnam
  • 2007-2011
    • Chosun University
      • College of Pharmacy
      Gwangju, Gwangju, South Korea
  • 2005-2010
    • Chungnam National University
      • College of Pharmacy
      Daiden, Daejeon, South Korea
  • 2006
    • Chungbuk National University
      Chinsen, Chungcheongbuk-do, South Korea