المؤلفون: Pen Yuan Chen, Chia Wei Lin, Chun Jung Chiu, Chia Li Wu, Li Ling Chi, Chung Yang Huang, Chia Nan Chen, Wei Jan Huang

المصدر: Cancer Letters. 291:108-119

مصطلحات موضوعية: Cancer Research, Cell growth, Poly ADP ribose polymerase, Cell Cycle, Apoptosis, Breast Neoplasms, Free Radical Scavengers, Biology, Cell cycle, Cyclin D1, Oncology, MCF-7, Biochemistry, Ethers, Cyclic, Cell culture, Caspases, Cell Line, Tumor, Bibenzyls, Humans, Female, Cyclin B1, Cell Proliferation

الوصف: Liverwort constituents have been reported to exert a broad spectrum of biological activities. In this study, we used a bioactivity-guided separation of an extract from the liverwort species Marchantia emarginata subsp. tosana to determine its anticancer activity. A high level of the active ingredient was isolated from this liverwort and its chemical structure was identified and characterized by various spectra. It was found to be identical to a well-known compound, marchantin A, a cyclic bisbibenzyl ether. However, no anticancer activities of this compound have previously been reported. We found that marchantin A efficiently induced cell growth inhibition in human MCF-7 breast cancer cells, with an IC(50) of 4.0microg/mL. Fluorescence microscopy and a Western blot analysis indicated that marchantin A actively induced apoptosis of MCF-7 cells. The levels of cleaved caspase-8, cleaved caspase-3, cleaved caspase-9, and cleaved poly (ADP ribose) polymerase (PARP) increased. However, the level of Bid markedly decreased in a dose- and time-dependent manner. We also evaluated the anticancer activities of marchantin A on the regulation of cell cycle regulators such as p21, p27, cyclin B1, and cyclin D1. The p21 and p27 gene expressions increased markedly while cyclin B1 and D1 gene expression decreased markedly by treatment with marchantin A. Many report demonstrated that liverwort was suggested to possess potent antioxidant activity. Our results indicate that marchantin A possesses free radical-scavenging activity (EC(50)=20microg/mL). Taken together, for the first time, the compound marchantin A from liverworts demonstrated to be a potent inducer of apoptosis in MCF-7 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b85e1f4617cee449876c1e252b9083eTest
https://doi.org/10.1016/j.canlet.2009.10.006Test

المؤلفون: Wei Jan Huang, Yue Wen Chen, Shuang En Chuang, Jen-Kun Lin, Chia Li Wu, Chung Yang Huang, Chia Nan Chen, Chun Liang Lin, Chih Hsiang Huang

المصدر: Journal of Agricultural and Food Chemistry. 55:7366-7376

مصطلحات موضوعية: Antioxidant, DPPH, medicine.medical_treatment, Taiwan, Apoptosis, medicine.disease_cause, Propolis, chemistry.chemical_compound, Coumarins, Cell Line, Tumor, medicine, Animals, Humans, Caspase, chemistry.chemical_classification, biology, Brain Neoplasms, Glioma, General Chemistry, Molecular biology, Rats, Enzyme, Biochemistry, chemistry, Cell culture, Caspases, Flavanones, biology.protein, Glioblastoma, General Agricultural and Biological Sciences, Oxidative stress

الوصف: We have previously shown that six propolins, A-F, could be isolated from Taiwanese propolis (TP) and that they exerted a broad spectrum of biological activities. Recently, we isolated a seventh compound, propolin G. Its chemical structure has been identified by NMR and fast atom bombardment-mass spectrometry spectra and was found to be identical to a known compound, nymphaeol C. We used high-performance liquid chromatography to determine the relative contents of propolins C, D, F, and G in TP collected in various seasons and regions and found them to be relatively higher in TPs collected from May to July than from September to October. In our present study, we were interested in the various biological activities of TP extract as well as in propolin G as a pure compound. We found that propolin G could efficiently induce apoptosis in brain cancer cell lines (glioma and glioblastoma). The apoptosis might have been through a mitochondrial- and caspase-dependent pathway. This result demonstrated that the TP collection season was more an important factor than the geographical region. Propolis has been suggested to possess a potent antioxidant activity. We further evaluated the antioxidant property of propolin G using DPPH (1,2-diphenyl-2-picryhydrazyl). Our results indicate that propolin G does possess free radical scavenging activity. We also evaluated the neuroprotective action of propolin G, TP, and BP (Brazilian propolis) extracts against oxidative stress in rat primary cortical neurons. Our data demonstrate that propolin G and TP extracts have a marked neuroprotective effect that is greater than BP extract. In conclusion, the isolation and characterization of propolin G from TP have demonstrated for the first time that this compound is a potent inducer of apoptosis in brain cancer cells and that this compound and TP extract exhibit a protective effect against oxidative stress in rat cortical neurons.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e6acae60d6cd9afa1c7b307072764aeeTest
https://doi.org/10.1021/jf0710579Test

المؤلفون: Chia-Nan Chen, Chia-Yun Hsu, Sheng-Yung Yu, Chung-Yang Huang, Jih-Tung Pai, Kuo Tai Hua, Meng-Shih Weng, Chiung-Ho Liao

المصدر: Molecules
Volume 20
Issue 5
Pages 8000-8019
Molecules, Vol 20, Iss 5, Pp 8000-8019 (2015)

مصطلحات موضوعية: Cyclin-Dependent Kinase Inhibitor p21, Proteasome Endopeptidase Complex, Cyclin E, Cell cycle checkpoint, Lung Neoplasms, Pharmaceutical Science, Down-Regulation, Biology, Histone Deacetylase 6, Hydroxamic Acids, Histone Deacetylases, Article, Analytical Chemistry, lcsh:QD241-441, Cyclin D1, lcsh:Organic chemistry, Coumarins, Cell Line, Tumor, Drug Discovery, NBM-T-BBX-OS01 (TBBX), Humans, HSP90 Heat-Shock Proteins, Physical and Theoretical Chemistry, heat shock protein 90, Cell Proliferation, Organic Chemistry, Cyclin-dependent kinase 2, Cyclin-Dependent Kinase 2, G1 Phase, Cyclin-Dependent Kinase 4, Acetylation, Cell Cycle Checkpoints, Cell cycle, suberoylanilide hydroxamic acid (SAHA), Hsp90, Up-Regulation, Histone Deacetylase Inhibitors, lung cancer, Proteasome, Chemistry (miscellaneous), cell cycle arrest, histone deacetylase, Cancer research, biology.protein, Molecular Medicine, CDK inhibitor

الوصف: Disrupting lung tumor growth via histone deacetylases (HDACs) inhibition is a strategy for cancer therapy or prevention. Targeting HDAC6 may disturb the maturation of heat shock protein 90 (Hsp90) mediated cell cycle regulation. In this study, we demonstrated the effects of semisynthesized NBM-T-BBX-OS01 (TBBX) from osthole on HDAC6-mediated growth arrest in lung cancer cells. The results exhibited that the anti-proliferative activity of TBBX in numerous lung cancer cells was more potent than suberoylanilide hydroxamic acid (SAHA), a clinically approved pan-HDAC inhibitor, and the growth inhibitory effect has been mediated through G1 growth arrest. Furthermore, the protein levels of cyclin D1, CDK2 and CDK4 were reduced while cyclin E and CDK inhibitor, p21Waf1/Cip1, were up-regulated in TBBX-treated H1299 cells. The results also displayed that TBBX inhibited HDAC6 activity via down-regulation HDAC6 protein expression. TBBX induced Hsp90 hyper-acetylation and led to the disruption of cyclin D1/Hsp90 and CDK4/Hsp90 association following the degradation of cyclin D1 and CDK4 proteins through proteasome. Ectopic expression of HDAC6 rescued TBBX-induced G1 arrest in H1299 cells. Conclusively, the data suggested that TBBX induced G1 growth arrest may mediate HDAC6-caused Hsp90 hyper-acetylation and consequently increased the degradation of cyclin D1 and CDK4.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ad1b59c429365a0ae74d9e130199a3d7Test
https://pubmed.ncbi.nlm.nih.gov/25946558Test

المؤلفون: Rong-Liang Zheng, Ji Li, Chung-Yang Huang, Kai-Rong Cui

المصدر: Molecular Biology Reports. 27:1-11

مصطلحات موضوعية: chemistry.chemical_classification, Reactive oxygen species, TUNEL assay, medicine.diagnostic_test, Wild type, food and beverages, General Medicine, Biology, Fas receptor, Molecular biology, Flow cytometry, Cell biology, Terminal deoxynucleotidyl transferase, chemistry, Apoptosis, Genetics, medicine, Signal transduction, Molecular Biology

الوصف: Reactive oxygen species (ROS) play an important role in cell death induced by many different stimuli. Direct exposure of human hepatoma cell line SMMC-7221 to hydrogen peroxide (H2O2) can induce apoptosis characterized by morphological evidence and fragmentation of DNA assayed by terminal deoxynucleotidyl transferase assay (TUNEL assay). Analysis of flow cytometry indicated that H2O2 can decrease the level of CD95(APO-1/Fas), and it is confirmed that H2O2 can also activate the differential expression of some specific gene such as p53 by means of RT-PCR technique. The results indicated that CD95 signal transduction system may be involved in the H2O2-induced apoptosis, and can regulate some specific genes associated with apoptosis in transcription and translation levels such as p53.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::fc1972212e5d7f1f5ac5c4ff80f78cf8Test
https://doi.org/10.1023/a:1007003229171Test

المؤلفون: Tung Hu Tsai, Jing Shi Huang, Wei Jan Huang, Chia Nan Chen, Ying Chen Yang, Carol Imei Wu, Chung Yang Huang, Tsun Yung Kuo, Ming Chung Kuan

المصدر: Evidence-Based Complementary and Alternative Medicine, Vol 2013 (2013)
Evidence-based Complementary and Alternative Medicine : eCAM

مصطلحات موضوعية: Gerontology, Article Subject, biology, Neurite, business.industry, HDAC8, Water maze, lcsh:Other systems of medicine, Pharmacology, biology.organism_classification, CREB, lcsh:RZ201-999, Cnidium monnieri, Complementary and alternative medicine, Neuroplasticity, biology.protein, Medicine, Memory impairment, Histone deacetylase, business, Research Article

الوصف: NBM-T-L-BMX-OS01 (BMX) was derived from the semisynthesis of osthole, isolated fromCnidium monnieri(L.) Cuss., and was identified to be a potent inhibitor of HDAC8. This study shows that HDAC8 is highly expressed in the pancreas and the brain. The function of HDAC8 in the brain has not been adequately studied. Because BMX enhances neurite outgrowth and cAMP response element-binding protein (CREB) activation, the effect of BMX on neural plasticity such as learning and memory is examined. To examine declarative and nondeclarative memory, a water maze, a passive one-way avoidance task, and a novel object recognition task were performed. Results from the water maze revealed that BMX and suberoylanilide-hydroxamic-acid-(SAHA-) treated rats showed shorter escape latency in finding the hidden platform. The BMX-treated animals spent more time in the target quadrant in the probe trial performance. An analysis of the passive one-way avoidance results showed that the BMX-treated animals stayed longer in the illuminated chamber by 1 day and 7 days after footshock. The novel object recognition task revealed that the BMX-treated animals showed a marked increase in the time spent exploring novel objects. Furthermore, BMX ameliorates scopolamine-(Sco-) induced learning and memory impairment in animals, indicating a novel role of BMX in learning and memory.

وصف الملف: text/xhtml

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::44bc50286268e3123568779acd55433cTest
https://doaj.org/article/31f658088db742b98f7a31d5138b6a50Test

المؤلفون: Wei Jan Huang, Li Ling Chi, Cheng Mike Yuan, Yue Wen Chen, Chung Yang Huang, Chia Nan Chen, Yu Cheng Kuo, Wei Jung Chen

المصدر: Journal of agricultural and food chemistry. 60(24)

مصطلحات موضوعية: food.ingredient, Pharmacology, Hydroxamic Acids, food, Western blot, Coumarins, Cell Line, Tumor, Royal jelly, Botany, medicine, Animals, Humans, Epigenetics, Gene, Glycoproteins, Regulation of gene expression, Vorinostat, biology, medicine.diagnostic_test, Queen bee, Fatty Acids, RNA-Binding Proteins, General Chemistry, Bees, biology.organism_classification, Rats, Worker bee, Histone Deacetylase Inhibitors, Gene Expression Regulation, Larva, Flavanones, Insect Proteins, Histone deacetylase, General Agricultural and Biological Sciences

الوصف: Royal jelly (RJ) is a widely used natural food. It is also a major source of nutrition for queen bees and plays a key role in their development. RJ is secreted from the hypopharyngeal and mandibular glands of young adult worker bees. The regulation of gene expression in these two glands may influence the development of queen bees by affecting the content of RJ. This study investigated the epigenetic effects in these two glands in young adult worker bees treated with histone deacetylase inhibitors (HDACis), a U.S. Food and Drug Administration-approved drug, suberoylanilide hydroxamic acid (SAHA), and NBM-HD-1, a novel compound synthesized in this laboratory. Western blot analyses indicated that the levels of acetyl-histone 3 and p21 protein expression in MCF-7 cells increased markedly after treatment with NBM-HD-1. The data proved that NBM-HD-1 was a novel and potent HDACi. Furthermore, a method of affecting epigenetic regulation of the mrjp family gene in the hypopharyngeal and mandibular glands of young adult worker bees was developed by feeding young adult worker bees HDACi. Epigenetic regulation produced several important biological effects. A marked change in the protein composition of the RJ secreted from these treated bees was found. Only the ratio of specific major royal jelly protein 3 (MRJP3) was significantly altered in the treated bees versus the untreated controls. Other MRJP family proteins did not change. This alteration in the ratio of royal jelly proteins resulted in a significant increase in the body size of queen bee larvae. The data seem to suggest that HDACis may play an important role in the epigenetic regulation of the hypopharyngeal and mandibular glands of young adult worker bees. They appear to change mrjp3 gene expression and alter the ratio of MRJP3 protein in RJ. This study presents the first evidence that HDACis are capable of regulating the ratio of MRJP3 proteins in RJ, which has the potential to change the body size of queen bees during their development.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5dcede642c8ff49d570eae743c0608fdTest
https://pubmed.ncbi.nlm.nih.gov/22642680Test

المؤلفون: Bi Lian Chiou, Chung Yang Huang, Hsien Ning Wang, Tzu Jung Chen, Chi Yun Lee, Chia Nan Chen, Yi Chen Chao, Chia Wei Lin, Li Ling Chi, Wei Jan Huang

المصدر: Journal of ethnopharmacology. 136(1)

مصطلحات موضوعية: medicine.drug_class, Antineoplastic Agents, Histone Deacetylases, Propolis, Flow cytometry, Western blot, Coumarins, Cell Line, Tumor, Drug Discovery, medicine, PTEN, Humans, Enzyme Inhibitors, Protein kinase B, Cell Proliferation, Pharmacology, medicine.diagnostic_test, biology, Histone deacetylase inhibitor, PTEN Phosphohydrolase, Glioma, Cell cycle, Biochemistry, Cell culture, Flavanones, biology.protein, Cancer research, Monoterpenes, Histone deacetylase, Glioblastoma, Proto-Oncogene Proteins c-akt

الوصف: Ethnopharmacological relevance Taiwanese green propolis (TGP) extract contains a variety of chemical components and has proven to have broad-spectrum biological activities, including anticancer, antioxidant, and antimicrobial activities. Propolin G, an active anticancer component of TGP, was isolated and characterized in this study. Histone deacetylase inhibitors (HDACis) have been shown to be effective anticancer agents. The aim of this study was to develop a novel HDACi and investigate its anticancer mechanism. Materials and methods NBM-HD-3, a novel HDACi, was derived from propolin G. Two brain cancer cell lines (c6 and DBTRG-05MG) were used in the anti-proliferation assay. NBM-HD-3 treated cells were analyzed by flow cytometry in the cell cycle assay. The gene expression of NBM-HD-3 treated cells was determined by real-time quantitative PCR. HDAC enzyme assay, confocal microscopy and Western blot assay were used to validate NMB-HD-3 as HDACi. Western blot assay was used for analyzing cell cycle modulation by PTEN and AKT. Results NBM-HD-3 was found to have potent anti-proliferative activity in brain cancer cells (rat C6 glioma and human DBTRG-05MG glioblastoma). Western blot analysis and HDAC enzyme assay indicated that NBM-HD-3 was an HDAC inhibitor. The Western blot data exhibited increased levels of p21, Ac-histone 3, Ac-histone 4, and Ac-tubulin after brain cancer cells being treated with NBM-HD-3. NBM-HD-3 also affected the cell cycle regulators such as p21 and cyclin B1. In the study for its anticancer mechanism, NBM-HD-3 was found to increase PTEN and AKT protein levels significantly, while decreasing p-PTEN and p-AKT levels markedly. Conclusion This study demonstrated that the novel compound, NBM-HD-3, is a potent HDAC inhibitor. It produces anticancer activity through modulation of PTEN and AKT in brain cancer cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a6ddf3e8c50b0abf93aba7d31428a9f7Test
https://pubmed.ncbi.nlm.nih.gov/21530633Test