Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Apoptosis
Type of Medium
Language
Year
  • 1
    Language: English
    In: PLoS ONE, 2012, Vol.7(5), p.e37764
    Description: Withanolides are a large group of steroidal lactones found in Solanaceae plants that exhibit potential anticancer activities. We have previously demonstrated that a withanolide, tubocapsenolide A, induced cycle arrest and apoptosis in human breast cancer cells, which was associated with the inhibition of heat shock protein 90 (Hsp90). To investigate whether other withanolides are also capable of inhibiting Hsp90 and to analyze the structure-activity relationships, nine withanolides with different structural properties were tested in human breast cancer cells MDA-MB-231 and MCF-7 in the present study. Our data show that the 2,3-unsaturated double bond-containing withanolides inhibited Hsp90 function, as evidenced by selective depletion of Hsp90 client proteins and induction of Hsp70. The inhibitory effect of the withanolides on Hsp90 chaperone activity was further confirmed using in vivo heat shock luciferase activity recovery assays. Importantly, Hsp90 inhibition by the withanolides was correlated with their ability to induce cancer cell death. In addition, the withanolides reduced constitutive NF-κB activation by depleting IκB kinase complex (IKK) through inhibition of Hsp90. In estrogen receptor (ER)-positive MCF-7 cells, the withanolides also reduced the expression of ER, and this may be partly due to Hsp90 inhibition. Taken together, our results suggest that Hsp90 inhibition is a general feature of cytotoxic withanolides and plays an important role in their anticancer activity.
    Keywords: Research Article ; Biology ; Medicine ; Molecular Biology ; Cell Biology ; Oncology ; Biochemistry
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(10), p.e0141184
    Description: In this study, six 2-phenylnaphthalenes with hydroxyl groups were synthesized in high yields by the demethylation of the corresponding methoxy-2-phenylnaphthalenes, and one 2-phenylnaphthalene with an amino group was obtained by hydrogenation. All of the 2-phenylnaphthalene derivatives were...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: PLoS ONE, 2012, Vol. 7(5), p. e37897
    Description: In a structure-activity relationship (SAR) study, 3-methoxy-1,4-phenanthrenequinones, calanquinone A (6a), denbinobin (6b), 5-OAc-calanquinone A (7a) and 5-OAc-denbinobin (7b), have significantly promising cytotoxicity against various human cancer cell lines (IC50 0.08-1.66 mu g/mL). Moreover, we also established a superior pharmacophore model for cytotoxicity (r = 0.931) containing three hydrogen bond acceptors (HBA1, HBA2 and HBA3) and one hydrophobic feature (HYD) against MCF-7 breast cancer cell line. The pharmacophore model indicates that HBA3 is an essential feature for the oxygen atom of 5-OH in 6a-b and for the carbonyl group of 5-OCOCH3 in 7a-b, important for their cytotoxic properties. The SAR for moderately active 5a-b (5-OCH3), and highly active 6a-b and 7a-b, are also elaborated in a spatial aspect model. Further rational design and synthesis of new cytotoxic phenanthrene analogs can be implemented via this model. Additionally, employing a ChemGPS-NP based model for cytotoxicity mode of action (MOA) provides support for a preliminary classification of compounds 6a-b as topoisomerase II inhibitors.
    Keywords: Medical And Health Sciences ; Medicin Och Hälsovetenskap
    ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Life Sciences, 2011, Vol.89(23), pp.886-895
    Description: Histone modifications play central epigenetic roles in regulating the entire genome of the cell and cell proliferation. Herein, we investigated the effects of the natural compound, 16-hydroxycleroda-3,13-dien-15,16-olide (PL3), on the expressions of histone-modifying enzymes, and examined how it induces apoptosis in leukemia K562 cells. Cell proliferation was determined by an MTT assay, and histone-modifying enzyme gene expressions were investigated by a quantitative real-time PCR. Protein expressions were analyzed by a Western blot analysis. The histone H3K27 distribution was observed with immunofluorescence staining. To verify polycomb repressive complex 2 (PRC2) complex downstream gene expressions, a gene-expression array was performed to determine gene regulations. PL3 induced apoptosis and modulated many histone-modifying enzymes, especially the two PRC2 components, enhancer of zeste homolog 2 (EZH2) and suppressor of zeste 12 homolog (Suz12). Genes repressed by PRC2 were shown to be reactivated by PL3. Of these, 10 genes targeted by the PRC2 complex were identified, and expressions of 10 pro-/antiapoptotic genes were significantly regulated; these effects may have contributed to PL3-induced apoptosis in K562 cells. Regulation of other histone-modifying enzymes, including Aurora B, may also be involved in cell-cycle regulation. Our data suggest that the induction of apoptosis by PL3 might partly occur through both a reduction in PRC2-mediated gene silencing and the reactivation of downstream tumor suppressor gene expressions. PL3 acts as a novel small-molecule histone modulator, which can potentially contribute to cancer chemotherapy singly or as a combined medication.
    Keywords: 16-Hydroxycleroda-3,13-Dien-15,16-Olide ; Apoptosis ; Histone Modulator ; Prc2 Complex ; Histone Modification ; Sciences (General) ; Biology
    ISSN: 0024-3205
    E-ISSN: 1879-0631
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: PLoS ONE, 01 January 2011, Vol.6(8), p.e23922
    Description: Protoapigenone, a natural flavonoid possessing an unusual p-quinol moiety on its B-ring, is a novel prospective anticancer agent with low toxicity that is currently in development. The first economical, one-step synthesis of protoapigenone from...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Angewandte Chemie International Edition, 16 August 2011, Vol.50(34), pp.7885-7891
    Description: : NMR spectroscopy and isothermal titration calorimetry show that calcium ions are chelated by the hydroxylated THF ring of acetogenins, which results in formation of complexes that aid the Ca cations in penetrating cell membranes and in elevating the intracellular calcium level (see picture). This disruption of intracellular calcium homeostasis induces mitochondrial depolarization and mediates cell toxicity.
    Keywords: Acetogenins ; Calcium ; Chelates ; Cytotoxicity ; Isothermal Titration Calorimetry
    ISSN: 1433-7851
    E-ISSN: 1521-3773
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Journal of agricultural and food chemistry, 27 April 2011, Vol.59(8), pp.4288-93
    Description: We evaluated the possible anticancer performance of a natural compound, goniothalamin (GTN), against human lung cancer using as a non-small cell lung cancer (NSCLC) cell line, H1299, as the model system. Cellular proliferation was significantly inhibited by GTN. Using an improved alkaline comet-nuclear extract (comet-NE) assay, GTN was found to induce a significant increase in the tail DNA. Wound healing and zymography assays showed that GTN attenuated cell migration and caused a reduction in the activity level of two major migration-associated matrix metalloproteinases, MMP-2 and MMP-9. It can be concluded that the DNA-damaging effect of GTN against lung cancer cells leads to growth inhibition as well as a depression in migration ability. Therefore, GTN has potential as a chemotherapeutic agent against lung cancer.
    Keywords: Apoptosis -- Drug Effects ; Carcinoma, Non-Small-Cell Lung -- Pathology ; Cell Division -- Drug Effects ; Cell Movement -- Drug Effects ; DNA Damage -- Drug Effects ; Lung Neoplasms -- Pathology ; Pyrones -- Pharmacology
    ISSN: 00218561
    E-ISSN: 1520-5118
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(5), p.e64739
    Description: BACKGROUND:Most chemotherapeutic drugs for killing cancer cells are highly cytotoxic in normal cells, which limits their clinical applications. Therefore, a continuing challenge is identifying a drug that is hypersensitive to cancer cells but has minimal deleterious effects on healthy cells....
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: BMC Cancer, 01 February 2011, Vol.11(1), p.58
    Description: Abstract Background Histone modifications in tumorigenesis are increasingly recognized as important epigenetic factors leading to cancer. Increased phosphorylation levels of histone H3 as a result of aurora B and pMSK1 overexpression were observed in various tumors. We selected aurora B and...
    Keywords: Medicine
    ISSN: 1471-2407
    E-ISSN: 1471-2407
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Life Sciences, 13 June 2013, Vol.92(22), pp.1081-1092
    Description: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. In this study, we explored the anti-cancer activity of WYC02-9, a synthetic protoapigenone, on human HCT116 CRC cells. The anti-cancer activity of WYC02-9 and its underlying mechanisms were analyzed using XTT cell proliferation assays, colony formation assays, FACS analysis, annexin V staining, immunoblotting analysis, reactive oxygen species (ROS) generation assays, soft agar assays, a nude mice xenograft study and immunohistochemistry assays. Data showed that WYC02-9 suppressed CRC cell growth by arresting cells at G2/M and inducing cell death via apoptotic pathways. Further analysis demonstrated that WYC02-9-induced apoptosis was mediated by the activation of a ROS-mediated MAPK14 pathway. An in vivo xenograft study revealed that WYC02-9 enhanced MAP2K3/6 and MAPK14 phosphorylation, induced apoptosis, and suppressed CRC tumor growth. WYC02-9 exerts its anti-tumor effect via ROS/MAPK14-induced apoptosis and has the potential to be developed as a chemotherapeutic agent for CRC.
    Keywords: Flavonoid ; Wyc02-9 ; Mapk14 ; Colorectal Cancer ; Sciences (General) ; Biology
    ISSN: 0024-3205
    E-ISSN: 1879-0631
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages