کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2127060 | 1086160 | 2017 | 11 صفحه PDF | دانلود رایگان |
Induction of potent apoptosis is required in cancer therapy. We examined the combination effect of interleukin-2-activated lymphocytes (LAK cells) and anticancer drugs or gamma (γ)-rays on the induction of apoptosis in an established oral squamous cell carcinoma cell line (OSC-3 cells). By pretreatment of OSC-3 cells with 137Cs (5 Gy), 5-fluorouracil (5-FU) (0.5 μg/ml) or cis-dichlorodiammine-platinum (CDDP) (5 μg/ml), the activation of bid and caspase-3 by LAK cells was strongly increased and associated with an enhanced degradation of poly-(ADP-ribose) polymerase (PARP) and/or nuclear mitotic apparatus protein (NuMA) and the increased fragmentation of DNA. The LAK cell–enhanced caspase-3 activity in the pretreated OSC-3 cells was decreased to approximately 70% and 40% of the control by the addition of Z-AAD-CMK (a granzyme B inhibitor) and neutralising monoclonal antibody to Fas antigen (αFas-IgG), respectively. The combined treatment-induced DNA fragmentation was suppressed by approximately 20% and 30% of the control by the addition of Z-AAD-CMK and αFas-IgG, respectively, in the co-culture system. While Ac-DEVD-CHO (a caspase-3 inhibitor) suppressed the DNA fragmentation levels to approximately half and this was similar to the amount of suppression that was obtained by the addition of both αFas-IgG and Z-AAD-CMK. In addition, LAK cell-activated bid may have increased the intracellular reactive oxygen intermediates (ROI) level and induced a decrease of mitochondrial membrane potential. These influences by LAK cells were enhanced when OSC-3 cells were pretreated with each anticancer drug or 137Cs. Furthermore, the increase of ROI by LAK cells was suppressed by αFas-IgG and Z-AAD-CMK to approximately half the level of the control. These results indicate that anticancer drugs and γ-rays prime squamous cell carcinoma cells to be susceptible to apoptosis by LAK cells, that LAK cell-induced apoptosis largely depends on the activation of caspase-3 by the Fas/Fas-ligand signal and granzyme B, and that LAK cells induce ROI in the target cells, which is largely mediated by Fas and granzyme B.
Journal: European Journal of Cancer - Volume 36, Issue 15, October 2000, Pages 2007–2017