| Nuclear permeable ruthenium(II) β-carboline complexes induce autophagy to antagonize mitochondrial-mediated apoptosis. | |
| | |
MedLine Citation:
|
PMID: 20958054 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The role of autophagy in cancer development and response to cancer therapy has been a subject of debate. Here we demonstrate that a series of ruthenium(II) complexes containing a β-carboline alkaloid as ligand can simultaneously induce autophagy and apoptosis in tumor cells. These Ru(II) complexes are nuclear permeable and highly active against a panel of human cancer cell lines, with complex 3 displaying activities greater than those of cisplatin. The antiproliferative potentialities of 1-3 are in accordance with their relative lipophilicities, cell membrane penetration abilities, and in vitro DNA binding affinities. Complexes 1-3 trigger release of reactive oxygen species (ROS) and attenuation of ROS by scavengers reduced the sub-G1 population, suggesting ROS-dependent apoptosis. Inhibition of ROS generation also reduces autophagy, indicating that ROS triggers autophagy. Further studies show that suppression of autophagy using pharmacological inhibitors (3-methyladenine and chloroquine) enhances apoptotic cell death. |
| | |
Authors:
|
Caiping Tan; Sensen Lai; Shouhai Wu; Sheng Hu; Lingjun Zhou; Yu Chen; Minxu Wang; Yiping Zhu; Wu Lian; Wenlie Peng; Liangnian Ji; Anlong Xu |
Related Documents
:
|
20237264 - Roles of nadph oxidases in cisplatin-induced reactive oxygen species generation and oto... 19361274 - Redox regulation of tumor necrosis factor signaling. 9654324 - Reactive oxygen species in the cellular pathophysiology of shock. 18506034 - Etosis: a novel cell death pathway. 10065364 - Modulation of drug metabolism in infectious and inflammatory diseases. 18287364 - White button mushroom enhances maturation of bone marrow-derived dendritic cells and th... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Journal of medicinal chemistry Volume: 53 ISSN: 1520-4804 ISO Abbreviation: J. Med. Chem. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-11-04 Completed Date: 2010-12-28 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 7613-24 Citation Subset: IM |
Affiliation:
|
State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antineoplastic Agents
/
chemical synthesis*,
chemistry,
pharmacology Apoptosis / drug effects* Autophagy / drug effects* Carbolines / chemical synthesis*, chemistry, pharmacology Cell Line, Tumor Cell Membrane Permeability Cell Nucleus / metabolism* Coordination Complexes / chemical synthesis*, chemistry, pharmacology DNA / chemistry Drug Screening Assays, Antitumor Green Fluorescent Proteins / genetics Humans Microscopy, Confocal Microscopy, Electron, Transmission Microtubule-Associated Proteins / genetics, metabolism Mitochondria / physiology* Reactive Oxygen Species / metabolism Ruthenium* Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Carbolines; 0/Coordination Complexes; 0/Microtubule-Associated Proteins; 0/Reactive Oxygen Species; 0/light chain 3, human; 147336-22-9/Green Fluorescent Proteins; 7440-18-8/Ruthenium; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Origin of lyotropic liquid crystalline mesophase formation and liquid crystalline to mesostructured ...
Next Document: Exploration of the active site of neuronal nitric oxide synthase by the design and synthesis of pyrr...