Inhibition of NF-κB activation by pvrrolidine dithiocarbamate increases sensitivity of HL-60 cells to cytotoxic drugs |
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| Authors: | CAO Wen-jing ZHANG Yao-zhen ZHANG Dong-hua LI Deng-ju TANG Jin-zhi |
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| Institution: | Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China |
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| Abstract: | AIM: To explore whether inhibition of NF-κB by antioxidant pvrrolidine dithiocarbamate (PDTC) sensitizes leukemia cells to cytotoxic drugs and its mechanism. METHODS: The indirect immunofluorescence method and electrophoretic mobility shift assay (EMSA) were used to measure the activation of NF-κB. The apoptotic cells were evaluated by flow cytometry (FCM) and the in vitro growth inhibitory effect was performed using a MTT assay. RESULTS: EMSA showed that NF-κB was activated by daunorubicin (DNR), VP-16 and then was inhibited by PDTC in a dose-dependent manner. NF-κB activation was further verified because of subunit RelA of NF-κB locating in the nuclei. FCM analysis showed that apoptotic index of HL-60 cells was up to (8.97±0.81)%, (16.01±1.06)%, (22.96±1.33)% from (5.34±0.62)%, (10.16±0.42)%, (17.32±1.15)% after exposure of HL-60 cells to 2.5-10 mg/L VP-16 combined with PDTC. VP-16 added with PDTC produced greater growth inhibitory effect to HL-60 cells than did VP-16 or DNR only (P<0.01). CONCLUSION: Reactive oxygen intermediates play an important role in inducible NF-κB activation. The inhibition of NF-κB by antioxidant PDTC sensitizes HL-60 cells to cytotoxic drugs. |
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