Ning-Sun Yang

Academia Sinica, T’ai-pei, Taipei, Taiwan

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Publications (71)227.48 Total impact

  • PLoS ONE 06/2015; 10(6):e0129067. DOI:10.1371/journal.pone.0129067
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    ABSTRACT: IL-12 p40, a common subunit for both IL-12 p70 and IL-23, plays a critical role in the development of Th1 and Th17 cells and autoimmune diseases. Regulation of IL-12 p40 expression is thus considered to be a strategy for developing therapies for Th1- and Th17-mediated autoimmune diseases. The mTOR protein is a subunit mTORC1 and mTORC2. Although mTORC1 has been shown to mediate IL-12 p40 expression in DCs and relevant signaling, the role of mTORC2 in IL-12 p40 expression remains largely unclear. In the present study, we demonstrate that blocking mTORC2 activity using the phytochemical cytopiloyne can specifically inhibit LPS-induced expression of IL-12 p70, IL-23, and IL-12 p40 in human DCs. This regulation by mTORC2 involving Akt activation and the persistent phase of NF-κB activation is further confirmed by siRNA knockdown of Rictor and Sin1 gene expression and the use of alternative inhibition approaches. In terms of IL-12 p40 expression, our findings reveal a new role for the mTORC2 pathway that is antagonistic to that of mTORC1. Our study provides new insight into mTOR regulation of IL-12 p40-mediated Th1 (IFN-γ) and Th17 (IL-17) responses and suggests that the phytochemical cytopiloyne might have useful applications in therapies for Th1 and Th17 cell-mediated inflammatory diseases. © Society for Leukocyte Biology.
    Journal of leukocyte biology 04/2015; 97(6). DOI:10.1189/jlb.2A0414-206RR
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    ABSTRACT: Curcuminoids, including curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), show the maximum absorption wavelength near blue light. Photodynamic therapy (PDT) has been developed as a therapeutic modality, which could induce cell death via the formation of ROS under illumination. Recently, it has been suggested that curcuminoids may be developed as potential photosensitizers. Here we found that curcuminoids-PDT significantly inhibited cell viability in breast cancer cell lines; in particular DMC-PDT has the highest anti-proliferative effect. A comprehensive analysis of cell response to DMC-PDT showed that autophagy was an early event and apoptosis was a late event. The generation of ROS by exciting the photosensitizer in PDT can activate MAPK pathway. Pre-treatment with a singlet oxygen scavenger or JNK inhibitor in DMC-PDT resulted in the reversion of cell viability, a reduced LC3 conversion and PARP cleavage. These results indicate that DMC may be considered as a new photosensitizer in PDT for cancer treatment.
    Journal of Functional Foods 01/2015; 12. DOI:10.1016/j.jff.2014.12.014
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    ABSTRACT: High expression of vimentin, a canonical mesenchymal marker, is linked with poor prognosis in triple negative breast cancer (TNBC), implying that vimentin may be a potential biomarker in the application of TNBC therapy. Pterostilbene (PTE) has shown anti-invasion activity, and thus, we investigated whether PTE inhibited the epithelial-mesenchymal transition (EMT) in TNBC. Here, we show that PTE decreases the vimentin expression, but that the effect was transient. PTE stimulated Fas signaling, which drives EMT by the ERK1/2 and GSK3β/β-catenin pathways, supporting Fas signaling induction involved in EMT regulation. PTE also triggered autophagy in TNBC. The treatment of TNBC with 3-methyladenine an autophagy inhibitor, not only sustained PTE-inhibited EMT but also significantly promoted anti-proliferation, which indicates that autophagy plays a cyto-protective role and is associated with EMT. Taken together, these data showed that Fas signaling and autophagy accelerated the aggressiveness of TNBC. Inhibition of autophagy or Fas signaling may provide novel targets for TNBC therapy.
    Food & Function 06/2014; 5(8). DOI:10.1039/c4fo00145a
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    ABSTRACT: Five new eunicellin-based diterpenoids, klymollins T-X (1-5), along with two known compounds (6 and 7) have been isolated from the soft coral Klyxum molle. The structures of these new metabolites were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. Compound 5 was found to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells. Furthermore, compounds 4 and 7 were shown to exhibit cytotoxicity against a limited panel of human cancer cell lines.
    Marine Drugs 05/2014; 12(5):3060-3071. DOI:10.3390/md12053060
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    ABSTRACT: Adjuvants can be used to enhance the immunogenicity of antigens and improve the efficacy of vaccines. Potent adjuvant action is known to often correlate with the activation of the transcription factor, nuclear factor-κB (NF-κB). Specific plant polysaccharides and a variety of phytochemicals from foods and traditional medicinal herbs have been shown to modulate NF-κB activation. In the present study, selected plant polysaccharides and phytochemicals were evaluated for use as a DNA vaccine adjuvant in a murine melanoma model. We observed that a specific ethanol extract fraction (DsCE-I) from the tuber of a key Traditional Chinese Medicine plant, Dioscorea ( Shān Yào), enhanced the protection against melanoma after immunization with a gene-based vaccine. A number of anti-inflammatory phytochemicals tested were able to partially diminish the inflammation-associated tumorigenesis elicited by LPS. Among the several phytochemical combinations investigated, the use of an adjuvant containing LPS in combination with emodin resulted in smaller tumors and higher survival rate in test mice than the use of other adjuvant treatments and the control sets in this DNA cancer vaccine model. A Dioscorea polysaccharide fraction (DsCE-I) and several specific phytochemicals warrant further exploration as useful adjuvants for anticancer vaccines.
    03/2014; 4(1):42-8. DOI:10.4103/2225-4110.124342
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    ABSTRACT: Triple negative breast cancer (TNBC) is defined by a lack of expression of the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER 2). Therefore, targeted therapy agents may not be used, and therapy is largely limited to chemotherapy. Doxorubicin-treatment consequently acquires undesired malignance characteristics (i.e., epithelial-mesenchymal transition (EMT) and multidrug resistance). Our results illustrated that doxorubicin triggered EMT and resulted in the acquisition of a mesenchymal phenotype in TNBC cells. Moreover, we found that TGF-β and PI3K/AKT signaling pathways were acquired for doxorubicin-induced EMT. Interestingly, we found that curcumin suppressed doxorubicin-induced EMT. Curcumin would reverse doxorubicin-induced morphological changes, up-regulate the expression of E-cadherin, and down-regulate the expression of vimentin. We also found that curcumin inhibited doxorubicin -induced EMT by inhibiting the TGF-β and PI3K/AKT signaling pathways. Moreover, curcumin enhanced the anti-proliferative effects of doxorubicin in TNBC cells. In summary, our results suggest that doxorubicin in combination with curcumin may be a potential therapy for TNBC.
    Journal of Agricultural and Food Chemistry 11/2013; 61(48). DOI:10.1021/jf404092f
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    ABSTRACT: This review reports details on the natural products isolated from Taiwan soft corals during the period 2008-2012 focusing on their in vitro and/or in vivo anti-inflammatory activities. Chemical structures, names, and literature references are also reported. This review provides useful and specific information on potent anti-inflammatory marine metabolites for future development of immune-modulatory therapeutics.
    Marine Drugs 10/2013; 11(10):4083-126. DOI:10.3390/md11104083
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    ABSTRACT: Yellow camellia, with its golden-yellow flowers, is rare in the world. Most studies of yellow camellia have focused on its ornamental properties; however, there were fewer published studies on its medical values. The purpose of this study was to define the chemical constituents and the biological potential of the water extract of leaves in six species of yellow camellia. Our data showed that Camellia murauchii had significantly higher total catechins and total polyphenol content than others; C. euphlebia had the highest total amino acids and γ-aminobutyric acid. Our results indicated that C. tunghinensis exhibited the highest free radical scavenging capacity and showed potent anticancer activities. C. nitidissima had stronger inhibitory effect than other species on fatty acid synthesis. In addition to catechins, 3-p-coumaroylquinic acid, kamepferol-3-O-glucoside and quercetin-3-O-glucoside were detected in C. tunghinensis using liquid chromatography tandem mass spectrometry. Taken together, yellow camellias possess biological activity and worthy of continued study.
    Journal of Agricultural and Food Chemistry 09/2013; 61(40). DOI:10.1021/jf4029877
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    ABSTRACT: Medicinal herbs and their derivative phytocompounds are being increasingly recognized as useful complementary treatments for cancer. A large volume of clinical studies have reported the beneficial effects of herbal medicines on the survival, immune modulation, and quality of life (QOL) of cancer patients, when these herbal medicines are used in combination with conventional therapeutics. Here, we briefly review some examples of clinical studies that investigated the use of herbal medicines for various cancers and the development of randomized controlled trials (RCTs) in this emerging research area. In addition, we also report recent studies on the biochemical and cellular mechanisms of herbal medicines in specific tumor microenvironments and the potential application of specific phytochemicals in cell-based cancer vaccine systems. This review should provide useful technological support for evidence-based application of herbal medicines in cancer therapy.
    Evidence-based Complementary and Alternative Medicine 07/2013; 2013:302426. DOI:10.1155/2013/302426
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    ABSTRACT: Dioscorea tuber phytoextracts can confer immunomodulatory activities ex vivo and improve regeneration of bone marrow cells in vivo. In present study, we evaluated specific Dioscorea phytoextracts for use ex vivo as a bone-marrow-derived dendritic cell- (DC-) based vaccine adjuvant for cancer immunotherapy. Fractionated Dioscorea extracts (DsII) were assayed for their effect on maturation and functions of DC ex vivo and antimelanoma activity of DC-based vaccine in vivo. The phytoextract from 50-75% ethanol-precipitated fraction of Dioscorea alata var. purpurea Tainung no. 5 tuber, designated as DsII-TN5, showed a strong augmentation of tumor cell lysate- (TCL-) loaded DC-mediated activation of T-cell proliferation. DsII-TN5 stimulated the expression of CD40, CD80, CD86, and IL-1 β in TCL-loaded DCs and downregulated the expression of TGF- β 1. DC vaccines prepared by a specific schema (TCL (2 h) + LPS (22 h)) showed the strongest antitumor activity. DsII-TN5 as a DC vaccine adjuvant showed strong antimelanoma activity and reduced myeloid-derived suppressor cell (MDSC) population in tested mice. DsII-TN5 can also activate DCs to enhance Th1- and Th17-related cytokine expressions. Biochemical analysis showed that DsII-TN5 consists mainly of polysaccharides containing a high level (53%) of mannose residues. We suggest that DsII-TN5 may have potential for future application as a potent, cost-effective adjuvant for DC-based cancer vaccines.
    Evidence-based Complementary and Alternative Medicine 07/2013; 2013:932040. DOI:10.1155/2013/932040
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    ABSTRACT: Although various pharmacological activities of the shikonins have been documented, understanding the hierarchical regulation of these diverse bioactivities at the genome level is unsubstantiated. In this study, through cross examination between transcriptome and microRNA array analyses, we predicted that topical treatment of shikonin in vivo affects epithelial-mesenchymal transition (EMT) and the expression of related microRNAs, including 200a, 200b, 200c, 141, 205, and 429 microRNAs, in mouse skin tissues. In situ immunohistological analyses further demonstrated that specific EMT regulatory molecules are enhanced in shikonin-treated epidermal tissues. RT-PCR analyses subsequently confirmed that shikonin treatment downregulated expression of microRNA-205 and other members of the 200 family microRNAs. Further, expression of two RNA targets of the 200 family microRNAs in EMT regulation, Sip1 (Zeb2) and Tcf8 (Zeb1), was consistently upregulated by shikonin treatment. Enhancement of these EMT activities was also detected in shikonin-treated wounds, which repaired faster than controls. These results suggest that topical treatment with shikonin can confer a potent stimulatory effect on EMT and suppress the expression of the associated microRNAs in skin wound healing. Collectively, these cellular and molecular data provide further evidence in support of our previous findings on the specific pharmacological effects of shikonin in wound healing and immune modulation.
    Evidence-based Complementary and Alternative Medicine 06/2013; 2013:262796. DOI:10.1155/2013/262796
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    ABSTRACT: Traditional medicinal herbs are increasingly used as alternative therapies in patients with inflammatory diseases. Here we evaluated the effect of Wedelia chinensis, a medicinal herb commonly used in Asia, on the prevention of dextran sulfate sodium (DSS)-induced acute colitis in mice. General safety and the effect of different extraction methods on the bioactivity of W. chinensis were also explored. C57BL/6 mice were administrated hot water extract of fresh W. chinensis (WCHF) orally for one week followed by drinking water containing 2% DSS for nine days. WCHF significantly attenuated the symptoms of colitis including diarrhea, rectal bleeding and loss of body weight; it also reduced the shortening of colon length and histopathological damage caused by colonic inflammation. Among four W. chinensis extracts prepared using different extraction techniques, WCHF showed the highest anti-colitis efficacy. Analyses of specific T-cell regulatory cytokines (TNF-α, IL-4, IFN-γ, IL-17, TGF-β, IL-12) revealed that WCHF treatment can suppress the Th1 and Th17, but not Th2, responses in colon tissues and dendritic cells of DSS-induced colitis mice. A 28-day subacute toxicity study showed that daily oral administration of WCHF (100, 500, 1000 mg/kg body weight) was not toxic to mice. Together, our findings suggest that specific extracts of W. chinensis have nutritional potential for future development into nutraceuticals or dietary supplements for treatment of inflammatory bowel disease.
    PLoS ONE 05/2013; 8(5):e64152. DOI:10.1371/journal.pone.0064152
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  • Kandan Aravindaram, Shu-Yi Yin, Ning-Sun Yang
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    ABSTRACT: A nonviral method for gene transfer into mammalian cells has been developed using physical force which accelerates plasmid DNA-coated gold particles to high -speed and penetrate the mammalian cells. This technology of gene transfer via a biolistic transfection method has been shown to have multiple applications to mammalian gene transfer systems. This method has also been adapted for delivery of other macromolecules like RNA, microRNA, and proteins. A broad range of somatic cell types, including primary cell cultures and established cell lines, have been successfully transfected ex vivo or in vitro by using the gene gun technology, either as suspension or adherent cells in cultures. This chapter describes the general procedures for in vitro DNA transfection by particle-mediated delivery to nonadherent and adherent cells. These procedures can be readily employed by using the Helios gene gun system (Bio-Rad, Hercules, CA) based on the Accell design.
    Methods in molecular biology (Clifton, N.J.) 01/2013; 940:133-43. DOI:10.1007/978-1-62703-110-3_11
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    ABSTRACT: Hematological malignancies frequently have a poor prognosis and often remain incurable. Drug resistance, severe side effects, and relapse are major problems of currently used drugs, and new candidate compounds are required for improvement of therapy success. The naphthoquinone shikonin derived from the Chinese medicinal herb, Lithospermum erythrorhizon, is a promising candidate for the next generation of chemotherapy. The basal cellular mechanism of shikonin is the direct targeting of mitochondria. Cytotoxicity screenings showed that the compound is particularly effective against leukemia cells suggesting an additional cellular mechanism. mRNA and miRNA microarrays were used to analyze changes in gene expression in leukemia cells after shikonin treatment and combined with stable-isotope dimethyl labeling for quantitative proteomics. The integration of bioinformatics and the three "-omics" assays showed that the PI3K-Akt-mTOR pathway was affected by shikonin. Deregulations of this pathway are frequently associated with cancerogenesis, especially in a wide range of hematological malignancies. The effect on the PI3K-Akt-mTOR axis was validated by demonstrating a decreased phosphorylation of Akt and a direct inhibition of the IGF1R kinase activity after shikonin treatment. Our results indicate that inhibiting the IGF1R-Akt-mTOR signaling cascade is a new cellular mechanism of shikonin strengthening its potential for the treatment of hematological malignancies.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:818709. DOI:10.1155/2013/818709
  • Kandan Aravindaram, Ning-Sun Yang
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    ABSTRACT: The metabolomic study of traditional Chinese medicine (TCM) and phytoextracts has been evaluated and is considered a useful and comprehensive strategy for assessing the integrated or combinatorial quality of herbal medicines. At present, several analytical platforms are employed, singularly and in combinations, to drive forward metabolomic research. These platforms include: gas chromatography (GC), high performance liquid chromatography (HPLC), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy. This chapter summarizes some of the metabolomic techniques most frequently used in phytomedicinal research against cancer, as well as the cytotoxic risks involved. We discuss the potential as well as the limitations of the various approaches. Multi-analyses techniques can partially overcome the shortcomings of single analysis-based techniques. With further development, especially in multi-analyses techniques, metabolomic studies are expected to advance TCM research in efficacy and toxicity, and to modernize TCM in terms of safety assessment and formulation, ultimately establishing the international standards to advance TCM laboratory research for the benefit of those at bedside.
    Biotechnology for Medicinal Plants, 01/2013: pages 275-294; , ISBN: 978-3-642-29973-5
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    ABSTRACT: Autoimmune diseases are the third largest category of illness in the industrialized world, following cardiovascular diseases and cancers. Among them, type 1 diabetes, also named autoimmune diabetes, afflicts 10 million people worldwide. This disease is caused by autoimmunity-mediated destruction of pancreatic-cells, leading to insulin deficiency, hyperglycemia and complications. Currently, there is no cure for type 1 diabetes. Insulin injection is the only medication; however, it accompanies serious medical complications. Current strategies to cure type 1 diabetes include immunotherapy, replacement therapy, and combination therapy. Despite recent advances in anti-diabetic strategies, no strategy is clinically successful. How to cure type 1 diabetes without undesirable side effects still remains a formidable challenge in drug research and development. Plants provide an extraordinary source of natural medicines for different diseases. Moreover, secondary metabolites of plant origin serve as an invaluable chemical library for drug discovery and current medicinal chemistry in the pharmaceutical industry. Over the past 25 years, 50% of prescription drugs have been developed from natural products and their derivatives. In this article, we review more than 20 plant compounds and extracts reported in the literature to prevent and treat type 1 diabetes. Emphasis is placed on their chemistry and biology in terms of regulation of immune cells and pancreatic-cells. We summarize recent progress in understanding of the biological actions, mechanisms and therapeutic potential of the compounds and extracts of plant origin in type 1 diabetes. New views on phytocompound-based strategies for prevention and treatment of type 1 diabetes are also discussed.
    Current Medicinal Chemistry 12/2012; DOI:10.2174/0929867311320070006
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    ABSTRACT: Colorectal cancer is a common malignancy and a leading cause of cancer death worldwide. Diet is known to play an important role in the etiology of colon cancer and dietary chemoprevention is receiving increasing attention for prevention and/or alternative treatment of colon cancers. Allium fistulosum L., commonly known as scallion, is popularly used as a spice or vegetable worldwide, and as a traditional medicine in Asian cultures for treating a variety of diseases. In this study we evaluated the possible beneficial effects of dietary scallion on chemoprevention of colon cancer using a mouse model of colon carcinoma (CT-26 cells subcutaneously inoculated into BALB/c mice). Tumor lysates were subjected to western blotting for analysis of key inflammatory markers, ELISA for analysis of cytokines, and immunohistochemistry for analysis of inflammatory markers. Metabolite profiles of scallion extracts were analyzed by LC-MS/MS. Scallion extracts, particularly hot-water extract, orally fed to mice at 50 mg (dry weight)/kg body weight resulted in significant suppression of tumor growth and enhanced the survival rate of test mice. At the molecular level, scallion extracts inhibited the key inflammatory markers COX-2 and iNOS, and suppressed the expression of various cellular markers known to be involved in tumor apoptosis (apoptosis index), proliferation (cyclin D1 and c-Myc), angiogenesis (VEGF and HIF-1α), and tumor invasion (MMP-9 and ICAM-1) when compared with vehicle control-treated mice. Our findings may warrant further investigation of the use of common scallion as a chemopreventive dietary agent to lower the risk of colon cancer.
    PLoS ONE 09/2012; 7(9):e44658. DOI:10.1371/journal.pone.0044658
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    ABSTRACT: Immunogenic cell death is characterized by damage-associated molecular patterns, which can enhance the maturation and antigen uptake of dendritic cells. Shikonin, an anti-inflammatory and antitumor phytochemical, was exploited here as an adjuvant for dendritic cell-based cancer vaccines via induction of immunogenic cell death. Shikonin can effectively activate both receptor- and mitochondria-mediated apoptosis and increase the expression of all five tested damage-associated molecular patterns in the resultant tumor cell lysates. The combination treatment with damage-associated molecular patterns and LPS activates dendritic cells to a high maturation status and enhances the priming of Th1/Th17 effector cells. Shikonin-tumor cell lysate-loaded mature dendritic cells exhibit a high level of CD86 and MHC class II and activate Th1 cells. The shikonin-tumor cell lysate-loaded dendritic cell vaccines result in a strong induction of cytotoxic activity of splenocytes against target tumor cells, a retardation in tumor growth, and an increase in the survival of test mice. The much enhanced immunogenicity and efficacy of the current cancer vaccine formulation, that is, the use of shikonin-treated tumor cells as cell lysates for the pulse of dendritic cells in culture, may suggest a new ex vivo approach for developing individualized, dendritic cells-based anticancer vaccines.
    Cancer Immunology and Immunotherapy 04/2012; DOI:10.1007/s00262-012-1258-9

Publication Stats

1k Citations
227.48 Total Impact Points

Institutions

  • 2002–2015
    • Academia Sinica
      • Agricultural Biotechnology Research Center
      T’ai-pei, Taipei, Taiwan
  • 2011
    • Medtronic
      Minneapolis, Minnesota, United States
  • 2001–2011
    • National Taiwan University
      • • Institute of Biotechnology
      • • Institute of Zoology
      • • School of Forestry and Resource Conservation
      T’ai-pei, Taipei, Taiwan
  • 2010
    • National Central University
      Taoyuan City, Taiwan, Taiwan