| Anthracenedione derivative 1403P-3 induces apoptosis in KB and KBv200 cells via reactive oxygen species-independent mitochondrial pathway and death receptor pathway. | |
| | |
MedLine Citation:
|
PMID: 17786034 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Anthracenedione derivatives are potent cytotoxic agents to tumor cells. In this study, we investigated the anticancer activities of anthracenedione derivative 1403P-3 separated from the secondary metabolites of the mangrove endophytic fungus No. 1403. Our results demonstrated that 1403P-3 showed potent cytotoxicity not only to human epidermoid carcinoma drug-sensitive parental KB cells but also to multidrug resistant (MDR) KBv200 cells and the IC50 values were 19.66 and 19.27 muM, respectively. Further research indicated that 1403P-3 induced apoptosis in KB cells and KBv200 cells confirmed by Hoechst 33258 staining, detection of DNA fragmentation and cleavage of poly (ADP-ribose) polymerase (PARP). Furthermore, apoptosis triggered by 1403P-3 was characterized by the loss of mitochondrial membrane potential (DeltaPsi(m)), release of cytochrome c, cleavage of Bid, and activation of caspases-2, -3, -7, -8 and -9. Z-IETD-FMK, caspase-8 inhibitor could inhibit the activation of caspase-2 and cleavage of Bid induced by 1403P-3. However, activation of caspase-9 and cleavage of PARP caused by 1403P-3 were not inhibited by Z-IETD-FMK. Additionally, 1403P-3 did not influence the expression level of Bcl-2 and Bax. It is noteworthy that 1403P-3 decreased the generation of reactive oxygen species (ROS) in KB cells and KBv200 cells. DNA binding assay exhibited that apoptosis induced by 1403P-3 was not involved in intercalating to DNA. In summary, 1403P-3 induced apoptosis of KB cells and KBv200 cells through mitochondrial pathway and death receptor pathway. Furthermore, the mitochondrial pathway was independent of reactive oxygen species and activation of caspase-8. |
| | |
Authors:
|
Jian-ye Zhang; Hai-ying Wu; Xue-kui Xia; Yong-ju Liang; Yan-yan Yan; Zhi-gang She; Yong-cheng Lin; Li-wu Fu |
Related Documents
:
|
10845254 - Myosin heavy chain degradation during apoptosis in endothelial cells. 20814064 - Superoxide is a potential culprit of caspase-3 dependent endothelial cell death induced... 11341974 - Docosahexaenoic acid induces apoptosis in jurkat cells by a protein phosphatase-mediate... 12851674 - Temporal ordering of caspase activation and substrate cleavage during antigen receptor-... 6288804 - Macrophage migration inhibition factor (mif): reducing the variables. 20711704 - The role of complement in amd. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-06-05 |
Journal Detail:
|
Title: Cancer biology & therapy Volume: 6 ISSN: 1555-8576 ISO Abbreviation: Cancer Biol. Ther. Publication Date: 2007 Sep |
Date Detail:
|
Created Date: 2008-01-11 Completed Date: 2008-05-28 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101137842 Medline TA: Cancer Biol Ther Country: United States |
Other Details:
|
Languages: eng Pagination: 1413-21 Citation Subset: IM |
Affiliation:
|
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Anthraquinones
/
chemistry*,
pharmacology Apoptosis BH3 Interacting Domain Death Agonist Protein / metabolism Caspases / metabolism Cell Line, Tumor Cell Survival DNA Fragmentation Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Humans Membrane Potentials Mitochondria / metabolism* Models, Biological Reactive Oxygen Species* Receptors, Death Domain / metabolism* |
| Chemical | |
Reg. No./Substance:
|
0/1403P-3 compound; 0/Anthraquinones; 0/BH3 Interacting Domain Death Agonist Protein; 0/Enzyme Inhibitors; 0/Reactive Oxygen Species; 0/Receptors, Death Domain; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Preclinical and clinical studies with the multi-kinase inhibitor CEP-701 as treatment for prostate c...
Next Document: A retrospective study on the quality of Haemophilus influenzae type b vaccines used in the UK betwee...