Hsin-Ling Yang

China Medical University Hospital, 臺中市, Taiwan, Taiwan

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Publications (55)171.52 Total impact

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    ABSTRACT: UVA irradiation-induced skin damage and redox imbalance have been shown to ameliorate by ergothioneine (EGT), a naturally occurring sulfur-containing amino acid. However, responsible molecular mechanism with nanomolar concentration of EGT remains unclear. We investigated the dermato-protective efficacies of EGT (125-500nM) against UVA irradiation (15J/cm(2)), and elucidated underlying molecular mechanism in human keratinocytes-derived HaCaT cells. We found that EGT treatment prior to UVA exposure significantly increased the cell viability and prevented lactate dehydrogenase release into the medium. UVA-induced ROS and comet-like DNA formation were remarkably suppressed by EGT with a parallel inhibition of apoptosis, as evidenced by reduced DNA fragmentation (TUNEL), caspase-9/-3 activation and Bcl-2/Bax dysregulation. Furthermore, EGT alleviated UVA-induced mitochondrial dysfunction. Dose-dependent increase of antioxidant genes, HO-1, NQO-1 and γ-GCLC, and glutathione by EGT were associated with up-regulated Nrf2 and down-regulated Keap-1 expressions. This was confirmed by increased nuclear accumulation of Nrf2 and inhibition of Nrf2 degradation. Notably, augmented luciferase activity of ARE may explain Nrf2/ARE-mediated signaling pathways behind EGT dermato-protective properties. We further demonstrated that Nrf2 translocation was mediated by PI3K/AKT, PKC or ROS signaling cascades. This phenomenon was confirmed with suppressed nuclear Nrf2 activation, and consequently diminished antioxidant genes in cells treated with respective pharmacological inhibitors (LY294002, GF109203X and N-acetylcysteine). Besides, increased basal ROS by EGT appears to be crucial for triggering the Nrf2/ARE signaling pathways. Silencing of Nrf2 or OCTN1 (EGT carrier protein) signaling with siRNA showed no such protective effects of EGT against UVA-induced cell death, ROS and apoptosis, which convinces the vitality of Nrf2 translocation and EGT protective efficacy in keratinocytes. Our findings conclude that EGT at nanomolar concentration effectively ameliorated the UVA-induced skin damage, and may consider as a desirable food supplement for skin protection and/or preparation of skin care products. Copyright © 2015. Published by Elsevier Inc.
    Free Radical Biology and Medicine 05/2015; DOI:10.1016/j.freeradbiomed.2015.05.026 · 5.71 Impact Factor
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    ABSTRACT: Although colorectal cancer (CRC) is one of the most common malignancies worldwide, the current therapeutic approaches for advanced CRC are ineffective. In this study, we investigated the involvement of the VAV3 oncogene in tumor progression and in the prognosis of human CRC. The two patient cohorts in this study comprised 354 CRC cases from 1998 to 2005 with documented pathologic and clinical factors and clinical outcomes. VAV3 protein levels were significantly correlated with the depth of invasion (P = 0.0259), the nodal status (P < 0.0001), distant metastasis (P = 0.0354), the stage (P < 0.0001), and poor disease-free survival (P = 0.003). Multivariate Cox regression analysis showed that VAV3 overexpression is an independent prognostic marker for CRC (P = 0.041). In vitro experiments indicated that VAV3 knockdown inhibited CRC cell growth, spread, and xenograft proliferation. Mechanistic studies further revealed that VAV3 overexpression could dysregulate the expression of cell cycle control- and metastasis-related molecules by activating the PI3K-AKT signaling pathway in both CRC cells and xenografts. This study suggests that VAV3 overexpression could be a useful marker for predicting the outcomes of CRC patients and that VAV3 targeting represents a potential modality for treating CRC.
    Scientific Reports 03/2015; 5:9360. DOI:10.1038/srep09360 · 5.58 Impact Factor
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    ABSTRACT: This study investigated the dermato-protective effects of lucidone, a cyclopentenedione from Lindera erythrocarpa dried fruits, against UVA-induced oxidative stress and apoptosis in human keratinocytes (HaCaT). Pre-treatment with lucidone (1–4 µM) significantly protects keratinocytes from UVA (15 J/cm2)-induced cell death, excessive ROS generation, LDH release, lipid peroxidation, and DNA damage. Notably, lucidone inhibited the UVA-induced apoptosis of HaCaT cells as measured by a reduction of DNA fragmentation, mitochondria dysfunction, and Bcl-2/Bax dysregulation. Furthermore, antioxidant potential of lucidone was directly correlated with the induction of antioxidant genes, including HO-1, NQO-1, and γ-GCLC by transcriptional activation of Nrf2. Treatment with hydrogen peroxide showed cellular byproducts of UVA irradiation-induced cell death, LDH release, and ROS generation, but these phenomena were inhibited by pre-treatment of lucidone. Besides, in Nrf2 knock-down cells, lucidone failed to protect UVA-induced oxidative stress or cell death. Our findings suggest that lucidone is capable of protecting skin cells from UVA-irradiated damage.
    Journal of Functional Foods 01/2015; 12. DOI:10.1016/j.jff.2014.10.019 · 4.48 Impact Factor
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    ABSTRACT: Antrodia salmonea (AS), a well-known medicinal mushroom in Taiwan, and has been reported to exhibit anti-oxidant, anti-angiogenic, anti-atherogenic, and anti-inflammatory effects. In the present study, we investigated the activation of Nrf2-mediated antioxidant genes in RAW264.7 macrophages by the fermented culture broth of AS, studied the resulting protection against lipopolysaccharide (LPS)-stimulated inflammation, and revealed the molecular mechanisms underlying these protective effects. We found that non-cytotoxic concentrations of AS (25-100 µg/mL) protected macrophages from LPS-induced cell death and ROS generation in a dose-dependent manner. The antioxidant potential of AS was directly correlated with the increased expression of the antioxidant genes HO-1, NQO-1, and γ-GCLC, as well as the level of intracellular GSH followed by an increase in the nuclear translocation and transcriptional activation of the Nrf2-ARE pathway. Furthermore, Nrf2 knockdown diminished the protective effects of AS, as evidenced by the increased production of pro-inflammatory cytokines and chemokines, including PGE2, NO, TNF-α, and IL-1β, in LPS-stimulated macrophages. Notably, AS treatment significantly inhibited the LPS-induced ICAM-1 expression in macrophages. Our data suggest that the anti-inflammatory potential of Antrodia salmonea mediated by the activation of Nrf2-dependent antioxidant defense mechanisms. Results support the traditional usage of this beneficial mushroom for the treatment of free radical-related diseases and inflammation.
    10/2014; 6(1). DOI:10.1039/C4FO00869C
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    ABSTRACT: Approximately 70% of the prostate cancer patients will develop bone metastasis in axial and other regions of the skeleton. Epidermal growth factor (EGF) generated from bone tissue contributes to prostate cancer metastasis. In our previous study, penta-O-galloyl-β-D-glucose (PGG) suppresses androgen-independent prostate cancer bone metastasis by transcriptionally repressing EGF-induced MMP-9 expression. In this study, we utilized the proteomics to analyze the effects of PGG in EGF-induced prostate cancer bone metastasis. Our study showed that PGG suppressed EGF-induced eIF3i expression in PC-3 cells. By transfection of eIF3i shRNA, we observed that reduced eIF3i expression suppressed the invasion of PC-3 cells in vitro. PGG reduced EGF-induced eIF3i expression through the inhibition of PI3K/AKT/mTOR pathway. Therefore, PGG may be able to apply in anticancer therapy and be used as a potential new therapeutic drug for prostate cancer bone metastasis.
    Journal of Agricultural and Food Chemistry 08/2014; 62(36). DOI:10.1021/jf502447e · 3.11 Impact Factor
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    ABSTRACT: Antrodia camphorata is a well-known medicinal mushroom in Taiwan. The broth from a fermented culture of Antrodia camphorata (AC) has been shown to induce apoptosis in cultured human premyelocytic leukemia (HL-60) cells. In the present study, we examined the effects of AC on cell cycle arrest in vitro in HL-60 cells and on tumor regression in vivo using an athymic nude mouse model. We found that AC (20-80 μg mL(-1)) treatment significantly induced G1 cell-cycle arrest in HL-60 cells by reducing the levels of cyclin D1, CDK4, cyclin E, CDK2, cyclin A, and phosphorylation of retinoblastoma protein (p-Rb). Moreover, AC treatment led to significantly increased protein expression levels of CDK inhibitors, including p21(WAF1) and p15(NIK4B). Additionally, AC treatment markedly induced intracellular ROS generation and mitochondrial dysfunction in HL-60 cells. Furthermore, the in vivo study results revealed that AC treatment was effective in terms of delaying the tumor incidence in nude mice that had been inoculated with HL-60 cells as well as in reducing the tumor burden. Histological analysis confirmed that AC treatment significantly modulated the xenografted tumor progression as demonstrated by a reduction in mitotic cells. Our data strongly suggest that Antrodia camphorata could be an anti-cancer agent for human leukemia.
    Food & Function 07/2014; 5(9). DOI:10.1039/c4fo00423j · 2.91 Impact Factor
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    ABSTRACT: The medicinal mushroom Antrodia salmonea has been used as a traditional Chinese medicine and has demonstrated antioxidant and anti-inflammatory effects. In the present study, we examined the anti-tumor activity of the fermented culture broth of Antrodia salmonea (AS) in vitro and in vivo and revealed its underlying molecular mechanism of action. Treatment of human promyelocytic leukemia (HL-60) cells with AS (50-150μg/mL) significantly reduced cell viability and caused G1 arrest via the inhibition of cell-cycle regulatory proteins, including cyclin D1, CDK4, cyclin E, cyclin A, and phosphorylated retinoblastoma protein (p-Rb). Furthermore, AS treatment induced apoptosis, which was associated with DNA fragmentation, followed by a sequence of events, including intracellular ROS generation; mitochondrial dysfunction; Fas ligand activation; cytochrome c release; caspase-3,-8, -9, and PARP activation; and Bcl-2/Bax dysregulation. The results of the in vitro study suggested that AS-induced apoptosis in HL-60 cells was mediated by both the mitochondrial and death receptor pathways. Furthermore, we found that AS treatment was effective in delaying tumor incidence in HL-60 xenografted nude mice and reducing tumor burden. To the best of our knowledge, this is the first report confirming the anti-tumor activity of this potentially beneficial mushroom against human promyelocytic leukemia.
    Journal of ethnopharmacology 03/2014; DOI:10.1016/j.jep.2014.03.012 · 2.94 Impact Factor
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    ABSTRACT: Toona sinensis is one of the most popular vegetarian cuisines in Taiwan and it has been shown to possess antioxidant, antiangiogenic, and anticancer properties. In this study, we investigated the antiatherosclerotic potential of aqueous leaf extracts from Toona sinensis (TS; 25-100 μg/mL) and its major bioactive compound, gallic acid (GA; 5 μg/mL), in LPS-treated rat aortic smooth muscle (A7r5) cells. We found that pretreatment with noncytotoxic concentrations of TS and GA significantly inhibited inflammatory NO and PGE2 production by downregulating their precursors, iNOS and COX-2, respectively, in LPS-treated A7r5 cells. Furthermore, TS and GA inhibited LPS-induced intracellular ROS and their corresponding mediator, p47(phox). Notably, TS and GA pretreatment significantly inhibited LPS-induced migration in transwell assays. Gelatin zymography and western blotting demonstrated that treatment with TS and GA suppressed the activity or expression of MMP-9, MMP-2, and t-PA. Additionally, TS and GA significantly inhibited LPS-induced VEGF, PDGF, and VCAM-1 expression. Further investigation revealed that the inhibition of iNOS/COX-2, MMPs, growth factors, and adhesion molecules was associated with the suppression of NF- κ B activation and MAPK (ERK1/2, JNK1/2, and p38) phosphorylation. Thus, Toona sinensis may be useful for the prevention of atherosclerosis.
    Oxidative Medicine and Cellular Longevity 03/2014; 2014:901315. DOI:10.1155/2014/901315 · 3.36 Impact Factor
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    ABSTRACT: Antrodia salmonea is well known in Taiwan as a beneficial mushroom. In the present study, we investigated the antioxidant activity of whole fermented broth (AS), filtrate (ASF), and mycelia (ASM) of Antrodia salmonea using different antioxidant models. Furthermore, the effect of Antrodia salmonea on AAPH-induced oxidative hemolysis of human erythrocytes and CuSO4-induced oxidative modification of human low-density lipoproteins (LDL) was examined. We found that the AS, ASF, and ASM possess effective antioxidant activity against various oxidative systems including superoxide anion scavenging, reducing power, metal chelation, and DPPH radical scavenging. Further, AAPH-induced oxidative hemolysis in erythrocytes was prevented by AS, ASF, and ASM. Notably, AS, ASF, and ASM appear to possess powerful antioxidant activities against CuSO4-induced oxidative modification of LDL as assessed by malondialdehyde (MDA) formation, cholesterol degradation, and the relative electrophoretic mobility of oxidized LDL. It is noteworthy that AS had comparatively strong antioxidant ability compared to ASF or ASM, which is well correlated with the content of their total polyphenols. Thus, Antrodia salmonea may exert antioxidant properties and offer protection from atherogenesis.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 01/2014; 66. DOI:10.1016/j.fct.2014.01.035 · 2.61 Impact Factor
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    ABSTRACT: Humic acid (HA) has been implicated as one of the etiological factors in the peripheral vasculopathy of blackfoot disease (BFD) in Taiwan. However, the underlying pathophysiological mechanisms of BFD are not well defined. In this study, we used an in vitro and in vivo model, in which HA (25-200μg/mL) activated macrophages to produce pro-inflammatory molecules by activating their transcriptional factors. HA exposure induced NO and PGE2 production followed by induction of iNOS and COX-2 through NF-κB/AP-1 transactivation in macrophages. In addition, the production of TNF-α and IL-1β was significantly increased by HA. Moreover, HA-induced iNOS and COX-2 expression were down-regulated by the NF-κB and AP-1 inhibitors pyrrolidine dithiocarbamate (PDTC) and Tanshinone, respectively. Furthermore, generations of ROS and nitrotyrosine, as well as activation of the AKT and MAPKs signaling cascades were observed after HA exposure. Specifically, HA-induced NF-κB activation was mediated by ROS and AKT, and that HA-induced AP-1 activation was mediated by JNK and ERK. Notably, HA-mediated AKT, JNK, and ERK activation was ROS-independent. The inflammatory potential of HA was correlated with increased expression of HO-1 and Nrf2. Furthermore, an in vivo study confirms that mice exposed to HA, the serum levels of TNF-α and IL-1β was significantly increased in a dose-dependent manner. This report marks the first confirmation that environmental exposure of HA induces inflammation in macrophages, which may be one of the main causes of early atherogenesis in blackfoot disease.
    Toxicology and Applied Pharmacology 11/2013; 274(2). DOI:10.1016/j.taap.2013.11.002 · 3.63 Impact Factor
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    ABSTRACT: Antrodia salmonea (AS) is known as a traditional Chinese medicine, but very few biological activities have been reported. The present study was aimed to investigate the anti-angiogenic and anti-atherosclerotic potential of the fermented culture broth of AS against tumor necrosis factor-α (TNF-α)-stimulated human endothelial (EA.hy 926) cells. The non-cytotoxic concentrations of AS significantly inhibited TNF-α-induced migration/invasion and capillary-like tube formation in EA.hy 926 cells. Furthermore, AS suppressed TNF-α-induced activity and expression of matrix metalloproteinase-9 (MMP-9), and cell-surface expression of intercellular adhesion molecule-1 (ICAM-1), which was associated with abridged adhesion of U937 leukocytes to endothelial cells. Moreover, AS significantly down-regulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor κB (NF-κB) followed by suppression of I-κB degradation and phosphorylation of I-κB kinase-α (IKKα). Notably, the protective effect of AS was directly correlated with the increased expression of hemeoxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCLC), which was reasoned by nuclear translocation and transactivation of NF-E2 related factor-2 (Nrf2)/antioxidant response element (ARE). Furthermore, HO-1 knockdown by HO-1-specific shRNA diminished the protective effects of AS on TNF-α-stimulated invasion, tube formation, and U937 adhesion in EA.hy 926 cells. Taken together, these results suggest that Antrodia salmonea may be useful for the prevention of angiogenesis and atherosclerosis.
    Journal of ethnopharmacology 11/2013; 151(1). DOI:10.1016/j.jep.2013.10.052 · 2.94 Impact Factor
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    ABSTRACT: Two new cardenolides, kalantubolide A (1) and kalantubolide B (2), and two bufadienolide glycosides, kalantuboside A (3) and kalantuboside B (4), as well as eleven known compounds were isolated and characterized from the EtOH extract of Kalanchoe tubiflora. The structures of compounds were assigned based on 1D and 2D NMR spectroscopic analyses including HMQC, HMBC, and NOESY. Biological evaluation indicated that cardenolides (1-2) and bufadienolide glycosides (3-7) showed strong cytotoxicity against four human tumor cell lines (A549, Cal-27, A2058, and HL-60) with IC50 values ranging from 0.01 µM to 10.66 µM. Cardenolides (1-2) also displayed significant cytotoxicity toward HL-60 tumor cell line. In addition, compounds 3, 4, 5, 6, and 7 blocked the cell cycle in the G2/M-phase and induced apoptosis in HL-60 cells.
    Planta Medica 07/2013; 79(14). DOI:10.1055/s-0033-1350646 · 2.34 Impact Factor
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    ABSTRACT: We investigated the protective effects of lucidone, a naturally occurring cyclopentenedione isolated from the fruits of Lindera erythrocarpa Makino, against free-radical and inflammation stimulator 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress in human keratinocyte (HaCaT) cells, with the aim of revealing the possible mechanisms underlying the protective efficacy. Lucidone pretreatment (0.5-10 μg/mL) markedly increased HaCaT cell viability and suppressed AAPH-induced reactive oxygen species (ROS) generation, lipid peroxidation, and DNA damage. Notably, the antioxidant potential of lucidone was directly correlated with the increased expression of an antioxidant gene, heme oxygenase 1 (HO-1), which was followed by the augmentation of the nuclear translocation and transcriptional activation of NF-E2-related factor-2 (Nrf2), with or without AAPH. Nrf2 knockdown diminished the protective effects of lucidone. We also observed that lucidone pretreatment inhibited AAPH-induced inflammatory chemokine prostaglandin E2 (PGE2) production and the expression of cyclooxygenase-2 (COX-2) in HaCaT cells. Lucidone treatment also significantly inhibited AAPH-induced nuclear factor-κB (NF-κB) activation and suppressing the degradation of inhibitor-κB (I-κB). Furthermore, lucidone significantly diminished AAPH-induced COX-2 expression through the down-regulation of the extracellular signal-regulated kinase (ERK) and p38 MAPK signaling pathways. Therefore, lucidone may possess antioxidant and anti-inflammatory properties and may be useful for the prevention of free radical-induced skin damage.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2013; 59. DOI:10.1016/j.fct.2013.04.055 · 2.61 Impact Factor
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    ABSTRACT: Gallic acid (GA) is a phenolic compound, which has been reported to suppress melanogenesis in melanoma cells. However, the molecular mechanism underlying this inhibitory effect was poorly understood. In this article, we revealed that GA down-regulated melanogenic regulatory genes including tyrosinase, tyrosinase related protein-1 (TRP-1), and dopachrome tatamerase (Dct) expression at transcriptional and translational level. In addition, GA effectively suppressed the microphthalmia-associated transcription factor (MITF) expression by down-regulating the cAMP-mediated PKA/CREB signaling cascades. To delineate the inhibition of MITF by GA, the activation of extracellular signal-regulated protein kinase (ERK) and AKT was investigated. GA caused significant increase of ERK and AKT phosphorylation, while ERK (PD98059) or AKT (LY294002) inhibitor prevents their phosphorylation and increased melanin biosynthesis. In addition, pre-treatment of MITF-siRNA significantly reduced melanin production from 100 to 40%, and even decreased into 10% by combination treatment with GA. Furthermore, UVB-induced hyperpigmentation in the mice skin was significantly rescued by topical application of GA for 4 weeks. Immunohistochemical analyses also confirmed that GA significantly inhibited melanin production followed by the down-regulation of MITF, tyrosinase and their regulatory proteins. In addition, when compared with control zebrafish, GA caused a remarkable inhibition on the endogenous pigmentation in the zebrafish. Results presented in this study strongly suggest that GA is an effective de-pigmenting or skin lightening cosmetics for topical application. © 2013 BioFactors, 2013.
    BioFactors 05/2013; 39(3). DOI:10.1002/biof.1064 · 3.00 Impact Factor
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    ABSTRACT: ETHNOPHARMACOLOGICAL RELAVENCE: Antrodia camphorata (AC) is well known in Taiwan as a traditional Chinese medicinal fungus. However, the anticancer activity of AC against human HER-2/neu-overexpressing ovarian cancers is poorly understood. MATERIALS AND METHODS: The aim of this study is to investigate whether a submerged fermentation culture of AC can inhibit human ovarian carcinoma cell (SKOV-3) proliferation by suppressing the HER-2/neu signaling pathway. Cell viability, colony formation, DCFH-DA fluorescence microscopy, western blotting, HER-2/neu immunofluorescence imaging, flow cytometry, and TUNEL assays were carried out to determine the anti-cancer effects of AC. RESULTS: MTT and colony formation assays showed that AC induced a dose-dependent reduction in SKOV-3 cell growth. Immunoblot analysis demonstrated that HER-2/neu activity and tyrosine phosphorylation were significantly inhibited by AC. Furthermore, AC treatment significantly inhibited the activation of PI3K/Akt and their downstream effector β-catenin. We also observed that AC caused G2/M arrest mediated by down-regulation of cyclin D1, cyclin A, cyclin B1, and Cdk1 and increased p27 expression. Notably, AC induced apoptosis, which was associated with DNA fragmentation, cytochrome c release, caspase-9/-3 activation, PARP degradation, and Bcl-2/Bax dysregulation. An increase in intracellular reactive oxygen species (ROS) was observed in AC-treated cells, whereas the antioxidant N-acetylcysteine (NAC) prevented AC-induced cell death, HER-2/neu depletion, PI3K/Akt inactivation, and Bcl-2/Bax dysregulation, indicating that AC-induced cell death was mediated by ROS generation. CONCLUSIONS: These results suggest that AC may exert anti-tumor activity against human ovarian carcinoma by suppressing HER-2/neu signaling pathways.
    Journal of ethnopharmacology 04/2013; 148(1). DOI:10.1016/j.jep.2013.04.023 · 2.94 Impact Factor
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    ABSTRACT: In the present study, we investigated the anti-inflammatory effects of a nutritious vegetable Toona sinensis (leaf extracts, TS) and its major bioactive compound gallic acid (GA) by analysing LPS-induced NF-κB activation in transgenic mice, using bioluminescence imaging. Mice were challenged intraperitoneally with LPS (1mg/kg) and treated orally with TS or GA (100 or 5mg/kg, respectively). In vivo and ex vivo imaging showed that LPS increased NF-κB luminescence in the abdominal region, which was significantly inhibited by TS or GA. Immunohistochemical and ELISA analyses confirmed that TS and GA inhibited LPS-induced NF-κB, interleukin-1β, and tumour necrosis factor-α expression. Microarray analysis revealed that biological pathways associated with metabolism and the immune responses were affected by TS or GA. Particularly, LPS-induced thioredoxin-like 4B (TXNL4B) 2 expression in the small intestine, and TXNL4B, iNOS, and COX-2 expression in RAW 264.7 cells were significantly inhibited by TS or GA. Thus, the anti-inflammatory potential of TS was mediated by the downregulation of NF-κB pathway.
    Food Chemistry 01/2013; 136(2):426-34. DOI:10.1016/j.foodchem.2012.08.009 · 3.26 Impact Factor
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    ABSTRACT: Antrodia camphorata (AC) is well known in Taiwan as a traditional Chinese medicine. The aim of this study was to investigate whether a fermented culture broth of AC could inhibit melanoma proliferation and progression via suppression of the Wnt/β-catenin signaling pathway. In this study, we observed that AC treatment resulted in decreased cell viability and disturbed Wnt/β-catenin cascade in B16F10 and/or B16F1 melanoma cells. This result was accompanied by a decrease in the expression of Wnt/β-catenin transcriptional targets, including c-Myc and survivin. Furthermore, treatment of melanoma cells with AC resulted in a significant increase in apoptosis, which was associated with DNA fragmentation, cytochrome c release, caspase-9 and -3 activation, PARP degradation, Bcl-2/Bax dysregulation, and p53 expression. We also observed that AC caused G(1) phase arrest mediated by a downregulation of cyclin D1 and CDK4 and increased p21 and p27 expression. In addition, we demonstrated that non- and subcytotoxic concentrations of AC markedly inhibited migration and invasion of highly metastatic B16F10 cells. The antimetastatic effect of AC was further confirmed by reductions in the levels of MMP-2, MMP-9, and VEGF expression. These results suggest that Antrodia camphorata may exert antitumor activity by downregulating the Wnt/β-catenin pathways.
    Evidence-based Complementary and Alternative Medicine 09/2012; 2012:197309. DOI:10.1155/2012/197309 · 1.88 Impact Factor
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    ABSTRACT: Four lanostane triterpenes, 3,7,11-trioxo-5α-lanosta-8,24(E)-dien-26-oic acid, methyl 11α-3,7-dioxo-5α-lanosta-8,24(E)-dien-26-oate, methyl 3,7,11,12,15,23-hexaoxo-5α-lanost-8-en-26-oate, and ethyl 3,7,11,12,15,23-hexaoxo-5α-lanost-8-en-26-oate, two sterols, (14α,22E)-14-hydroxyergosta-7,22-diene-3,6-dione and a steroid named as camphosterol A were isolated from a mixture of fruiting bodies and mycelia of solid cultures of Antrodia camphorata. The 1H and 13C NMR spectra of all compounds were fully assigned using a combination of 2D NMR experiments, including COSY, HMQC, HMBC and NOESY sequences. Six compounds were evaluated for cytotoxicity against several human tumor cell lines, all of which has moderate activity.
    Phytochemistry 09/2012; 84:177–183. DOI:10.1016/j.phytochem.2012.08.011 · 3.35 Impact Factor
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    ABSTRACT: Toona sinensis is one of the most popular vegetarian cuisines in Taiwan and it has been shown to induce apoptosis in cultured human premyelocytic leukemia (HL-60) cells. In the present study, we examined the effects of T. sinensis leaf extracts (TS extracts) on tumor regression using in vitro cell culture and an in vivo athymic nude mice model. We found that TS extracts (10-75μg/mL) arrested HL-60 cells at the G(1)-S transition phase through the reductions of Cyclin D1, CDK4, Cyclin E, CDK2, and Cyclin A, and induction of CDK inhibitor p27(KIP) levels. Furthermore, VEGF expression and release was significantly inhibited by TS extracts. Notably, TS extracts treatment was effective in terms of delaying tumor incidence in the nude mice inoculated with HL-60 cells as well as reducing the tumor burden. Histological analysis confirmed that TS extracts significantly modulated tumor progression in xenograft tumor. Furthermore, a similar pattern of results were observed from gallic acid (5 and 10μg/mL), a major compound in TS, caused G(1) arrest through regulations of cell-cycle regulatory proteins. Our data suggest that T. sinensis exerts antiproliferative effects on HL-60 cells in vitro and in vivo due mainly to the presence of gallic acid.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 07/2012; 50(10):3489-97. DOI:10.1016/j.fct.2012.06.046 · 2.61 Impact Factor
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    ABSTRACT: Previously, we demonstrated that a submerged fermentation culture of Antrodia camphorata (AC) promotes cell-cycle arrest and apoptosis in human estrogen receptor-positive/negative breast cancer cells. However, whether AC is effective against HER-2/neu-overexpressing breast cancers has not been thoroughly elucidated. In the present study, we showed that AC exhibited a significant cytotoxic effect against HER-2/neu-overexpressing MDA-MB-453 and BT-474 cells. Immunoblot analysis demonstrated that HER-2/neu and their tyrosine phosphorylation were inhibited by AC in a dose-dependent manner. An increase in intracellular reactive oxygen species (ROS) was observed in AC-treated cells, whereas antioxidant N-acetylcysteine (NAC) significantly prevented AC induced HER-2/neu depletion and cell death, which directly indicates that AC-induced HER-2/neu depletion and cell death was mediated by ROS generation. Also, AC significantly downregulated the expression of cyclin D1, cyclin E, and CDK4 followed by the suppression of PI3K/Akt, and their downstream effectors GSK-3β and β-catenin. Notably, AC-treatment induced apoptotic cell death, which was associated with sub-G1 accumulation, DNA fragmentation, mitochondrial dysfunction, cytochrome c release, caspase-3/-9 activation, PARP degradation, and Bcl-2/Bax dysregulation. Assays for colony formation also confirmed the growth-inhibitory effects of AC. This is the first report confirming the anticancer activity of this potentially beneficial mushroom against human HER-2/neu-overexpressing breast cancers.
    Evidence-based Complementary and Alternative Medicine 06/2012; 2012(1741-427X):702857. DOI:10.1155/2012/702857 · 1.88 Impact Factor

Publication Stats

985 Citations
171.52 Total Impact Points

Institutions

  • 2002–2015
    • China Medical University Hospital
      • Department of Radiology
      臺中市, Taiwan, Taiwan
  • 2006–2014
    • China Medical University (ROC)
      臺中市, Taiwan, Taiwan
  • 2013
    • University of Texas MD Anderson Cancer Center
      • Department of Molecular and Cellular Oncology
      Houston, Texas, United States