Document Detail


Lgf-YL-9 induces apoptosis in human epidermoid carcinoma KB cells and multidrug resistant KBv200 cells via reactive oxygen species-independent mitochondrial pathway.
MedLine Citation:
PMID:  17055640     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pyrazolon derivatives were reported to have cytotoxicity to some tumour cells. In the present study, we investigated the effect of Lgf-YL-9 on cytotoxicity and cell apoptosis in human epidermoid carcinoma drug-sensitive parental KB cells and multidrug resistant (MDR) KBv200 cells. Lgf-YL-9 exhibited potent cytotoxicity not only to KB cells but also to KBv200 cells, and the IC(50) were 3.81 and 3.45 microg/mL in KB cells and KBv200 cells, respectively. Importantly, Lgf-YL-9 effectively inhibited tumour growth of KB cell xenografts in nude mice. Lgf-YL-9-induced cell apoptosis was confirmed by chromatin condensation, DNA fragmentation, Annexin-V and propidium iodide (PI) double-staining assay and poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, Lgf-YL-9-mediated apoptosis in KB cells and KBv200 cells was accompanied by the loss of mitochondrial membrane potential (DeltaPsi(m)), the release of cytochrome c, and the activation of caspases-3, -7, and -9, but not by intercalating to DNA. Although Lgf-YL-9-induced apoptosis was associated with the decrease of DeltaPsi(m), reactive oxygen species (ROS) reduction was interestingly observed in both cell lines. The data suggest that Lgf-YL-9 has similar cytotoxicity to drug-sensitive parental KB cells and MDR KBv200 cells. Lgf-YL-9-induced apoptosis is involved in a new ROS-independent mitochondrial dysfunction pathway, but not in intercalating to DNA.
Authors:
Xiao-Hong Wang; Dian-Zeng Jia; Yong-Ju Liang; Su-Li Yan; Yan Ding; Li-Ming Chen; Zhi Shi; Mu-Sheng Zeng; Guang-Fei Liu; Li-Wu Fu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-20
Journal Detail:
Title:  Cancer letters     Volume:  249     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-03-27     Completed Date:  2007-06-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  256-70     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, PR China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Survival / drug effects
Cytochromes c / metabolism
DNA / metabolism
DNA Fragmentation
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Female
Humans
KB Cells
Male
Membrane Potential, Mitochondrial / drug effects
Mice
Mice, Nude
Pyrazolones / pharmacology*
Reactive Oxygen Species / metabolism
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Pyrazolones; 0/Reactive Oxygen Species; 9007-43-6/Cytochromes c; 9007-49-2/DNA

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