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  • Title: Lgf-YL-9 induces apoptosis in human epidermoid carcinoma KB cells and multidrug resistant KBv200 cells via reactive oxygen species-independent mitochondrial pathway.
    Author: Wang XH, Jia DZ, Liang YJ, Yan SL, Ding Y, Chen LM, Shi Z, Zeng MS, Liu GF, Fu LW.
    Journal: Cancer Lett; 2007 May 08; 249(2):256-70. PubMed ID: 17055640.
    Abstract:
    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.
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