Lgf-YL-9 induces apoptosis in human epidermoid carcinoma KB cells and multidrug resistant KBv200 cells via reactive oxygen species-independent mitochondrial pathway
| Autor: | Yan Ding, Guang fei Liu, Li Wu Fu, Zhi Shi, Mu Sheng Zeng, Dian zeng Jia, Xiao Hong Wang, Li Ming Chen, Su Li Yan, Yong Ju Liang |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Cancer Research Cell Survival Poly ADP ribose polymerase Mice Nude Antineoplastic Agents Apoptosis DNA Fragmentation Biology KB Cells Mice chemistry.chemical_compound Animals Humans Propidium iodide Pyrazolones Cytotoxicity P-glycoprotein Membrane Potential Mitochondrial Cytochromes c DNA Xenograft Model Antitumor Assays Molecular biology Drug Resistance Multiple Oncology Epidermoid carcinoma chemistry Drug Resistance Neoplasm Cell culture biology.protein DNA fragmentation Female Reactive Oxygen Species |
| Zdroj: | Cancer Letters. 249:256-270 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2006.09.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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