hyperforin has been researched along with Neoplasms* in 5 studies
1 review(s) available for hyperforin and Neoplasms
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Hyperforin, a new lead compound against the progression of cancer and leukemia?
Extracts of the plant St John's wort, Hyperforin perforatum L., have been used for centuries in traditional medicine, notably for the treatment of depression. One of their main lipophilic components, a natural prenylated phloroglucinol termed hyperforin (HF), has been identified as the major molecule responsible for the antidepressant effects of this plant. Within the last few years, a number of studies have demonstrated that HF displays, in addition, several other biological properties of potential pharmacological interest. They include an antibacterial capacity and inhibitory effects on inflammatory mediators. It is worth noting that HF also promotes apoptosis of various cancer cells from solid tumors and hematological malignancies, including B-cell chronic lymphocytic leukemia. In addition, HF inhibits the capacity of migration and invasion of different tumor cells, as well as exhibiting antiangiogenic effects. Altogether, these properties qualify HF as a lead structure for the development of new therapeutic molecules in the treatment of various diseases, including some malignant tumors. Topics: Anti-Infective Agents; Antidepressive Agents; Antineoplastic Agents; Bridged Bicyclo Compounds; Humans; Neoplasms; Phloroglucinol; Terpenes | 2006 |
4 other study(ies) available for hyperforin and Neoplasms
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Tetrahydrohyperforin Inhibits the Proteolytic Processing of Amyloid Precursor Protein and Enhances Its Degradation by Atg5-Dependent Autophagy.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) peptide. We have previously shown that the compound tetrahydrohyperforin (IDN5706) prevents accumulation of Aβ species in an in vivo model of AD, however the mechanism that explains this reduction is not well understood. We show herein that IDN5706 decreases the levels of ER degradation enhancer, mannosidase alpha-like 1 (EDEM1), a key chaperone related to endoplasmic-reticulum-associated degradation (ERAD). Moreover, we observed that low levels of EDEM1 correlated with a strong activation of autophagy, suggesting a crosstalk between these two pathways. We observed that IDN5706 perturbs the glycosylation and proteolytic processing of the amyloid precursor protein (APP), resulting in the accumulation of immature APP (iAPP) in the endoplasmic reticulum. To investigate the contribution of autophagy, we tested the effect of IDN5706 in Atg5-depleted cells. We found that depletion of Atg5 enhanced the accumulation of iAPP in response to IDN5706 by slowing down its degradation. Our findings reveal that IDN5706 promotes degradation of iAPP via the activation of Atg5-dependent autophagy, shedding light on the mechanism that may contribute to the reduction of Aβ production in vivo. Topics: Amyloid beta-Protein Precursor; Animals; Autophagy; Autophagy-Related Protein 5; Blotting, Western; Cells, Cultured; Endoplasmic Reticulum; Fibroblasts; Fluorescent Antibody Technique; Glycosylation; Humans; Immunoenzyme Techniques; Immunoprecipitation; Kidney; Membrane Proteins; Microscopy, Fluorescence; Microtubule-Associated Proteins; Neoplasms; Phloroglucinol; Protein Processing, Post-Translational; Proteolysis; Rats; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Terpenes; TOR Serine-Threonine Kinases | 2015 |
Mechanisms of Hyperforin as an anti-angiogenic angioprevention agent.
Hyperforin, the major lipophilic compound contained in extracts of Hypericum perforatum, is responsible for the antidepressant activity associated with the extract. Recently, several other biological properties of Hyperforin have been unveiled including inhibition of tumour invasion and angiogenesis. The mechanism of the anti-angiogenic activity of Hyperforin remains to be fully elucidated. We show that treatment with non-cytotoxic concentrations of Hyperforin restrains, in a dose-dependent manner, the capacity of endothelial cells to migrate towards relevant chemotactic stimuli. Hyperforin inhibits the organisation of HUVE endothelial cells in capillary-like structures in vitro, and potently represses angiogenesis in vivo in the Matrigel sponge assay in response to diverse angiogenic agents. Immunofluorescent staining shows that in cytokine-activated endothelial HUVE cells Hyperforin prevents translocation to the nucleus of NF-kappaB, a transcription factor regulating numerous genes involved in cell growth, survival, angiogenesis and invasion. Under Hyperforin treatment in vivo, the growth of Kaposi's sarcoma - a highly angiogenic tumour - is strongly inhibited, with the resultant tumours remarkably reduced in size and in vascularisation as compared with controls. Hyperforin has also been reported to have anti-inflammatory properties. Here we show that Hyperforin inhibits neutrophil and monocyte chemotaxis in vitro and angiogenesis in vivo induced by angiogenic chemokines (CXCL8 or CCL2). These results highlight the potential for Hyperforin as an anti-inflammatory angioprevention agent, acting as a strong inhibitor of inflammation- or tumour-triggered angiogenesis, and provide new therapeutic approaches to halting pathology-associated angiogenesis. Topics: Analysis of Variance; Angiogenesis Inhibitors; Animals; Apoptosis; Bridged Bicyclo Compounds; Cell Line, Tumor; Cell Movement; Endothelial Cells; Humans; Male; Mice; Mice, Nude; Microscopy, Fluorescence; Neoplasms; Neovascularization, Pathologic; Phloroglucinol; Terpenes; Xenograft Model Antitumor Assays | 2009 |
Hyperforin inhibits cancer invasion and metastasis.
Hyperforin (Hyp), the major lipophilic constituent of St. John's wort, was assayed as a stable dicyclohexylammonium salt (Hyp-DCHA) for cytotoxicity and inhibition of matrix proteinases, tumor invasion, and metastasis. Hyp-DCHA triggered apoptosis-associated cytotoxic effect in both murine (C-26, B16-LU8, and TRAMP-C1) and human (HT-1080 and SK-N-BE) tumor cells; its effect varied, with B16-LU8, HT-1080, and C-26 the most sensitive (IC50 = 5 to 8 micromol/L). At these concentrations, a marked and progressive decline of growth was observed in HT-1080 cells, whereas untransformed endothelial cells were only marginally affected. Hyp-DCHA inhibited in a dose-dependent and noncompetitive manner various proteinases instrumental to extracellular matrix degradation; the activity of leukocyte elastase was inhibited the most (IC50 = 3 micromol/L), followed by cathepsin G and urokinase-type plasminogen activator, whereas that of the matrix metalloproteinases (MMPs) 2 and 9 showed an IC50 > 100 micromol/L. Nevertheless, inhibition of extracellular signal-regulated kinase 1/2 constitutive activity and reduction of MMP-2 and MMP-9 secretion was triggered by 0.5 micromol/L Hyp-DCHA to various degrees in different cell lines, the most in C-26. Inhibition of C-26 and HT-1080 cell chemoinvasion (80 and 54%, respectively) through reconstituted basement membrane was observed at these doses. Finally, in mice that received i.v. injections of C-26 or B16-LU8 cells, daily i.p. administration of Hyp-DCHA-without reaching tumor-cytotoxic blood levels-remarkably reduced inflammatory infiltration, neovascularization, lung weight (-48%), and size of experimental metastases with C-26 (-38%) and number of lung metastases with B16-LU8 (-22%), with preservation of apparently healthy and active behavior. These observations qualify Hyp-DCHA as an interesting lead compound to prevent and contrast cancer spread and metastatic growth. Topics: Adenocarcinoma; Animals; Apoptosis; Bridged Bicyclo Compounds; Cell Division; Cell Survival; Colonic Neoplasms; Cyclohexylamines; Enzyme Activation; Fibrosarcoma; Gelatinases; Humans; Lung Neoplasms; Male; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neuroblastoma; Phloroglucinol; Quaternary Ammonium Compounds; Serine Endopeptidases; Terpenes | 2004 |
Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis.
Hyperforin is a plant derived antibiotic from St. John's wort. Here we describe a novel activity of hyperforin, namely its ability to inhibit the growth of tumour cells by induction of apoptosis. Hyperforin inhibited the growth of various human and rat tumour cell lines in vivo, with IC(50) values between 3-15 microM. Treatment of tumour cells with hyperforin resulted in a dose-dependent generation of apoptotic oligonucleosomes, typical DNA-laddering and apoptosis-specific morphological changes. In MT-450 mammary carcinoma cells hyperforin increased the activity of caspase-9 and caspase-3, and hyperforin-mediated apoptosis was blocked by the broad-range caspase inhibitor zVAD.fmk. When added to MT-450 cells, hyperforin, but not paclitaxel, induced a rapid loss of the mitochondrial transmembrane potential Deltapsi(m), and subsequent morphological changes such as homogenization and vacuolization of mitochondria. Monitoring of Deltapsi(m) revealed that the hyperforin-mediated mitochondrial permeability transition can not be prevented by zVAD.fmk. This indicates that mitochondrial permeabilization is a cause rather than a consequence of caspase activation. Moreover, hyperforin was capable of releasing cytochrome c from isolated mitochondria. These findings suggest that hyperforin activates a mitochondria-mediated apoptosis pathway. In vivo, hyperforin inhibited the growth of autologous MT-450 breast carcinoma in immunocompetent Wistar rats to a similar extent as the cytotoxic drug paclitaxel, without any signs of acute toxicity. Owing to the combination of significant antitumour activity, low toxicity in vivo and natural abundance of the compound, hyperforin holds the promise of being an interesting novel antineoplastic agent that deserves further laboratory and in vivo exploration. Topics: Animals; Antineoplastic Agents; Apoptosis; Bridged Bicyclo Compounds; Caspases; Cell Division; Cytochrome c Group; Dose-Response Relationship, Drug; Enzyme Activation; Female; Humans; Hypericum; Intracellular Membranes; Microscopy, Electron; Mitochondria; Neoplasms; Phloroglucinol; Rats; Staurosporine; Terpenes; Time Factors; Tumor Cells, Cultured | 2002 |