Caspase-3 activation as a key factor for HBx-transformed cell death

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Caspase-3 activation as a key factor for HBx-transformed cell death
A Kim; O S Kwon; S O Kim; L He; E Y Bae; M S Lee; S J Jeong; J H Shim; D Y Yoon; C H Kim; A Moon; K E Kim; Jong Seog AhnBo Yeon Kim
Bibliographic Citation
Cell Proliferation, vol. 41, no. 5, pp. 755-774
Publication Year
Objectives: Nuclear factor-kappa B (NF-κB) activation has been associated with the tumorigenic growth of hepatitis B virus X protein (HBx)-transformed cells. This study was aimed to find a key target for treatment of HBx-mediated cancers. Materials and methods: NF-κB activation, endoplasmic reticulum-stress (ER-stress), caspase-3 activation, and cell proliferation were evaluated after Chang/HBx cells permanently expressing HBx viral protein were treated with inhibitors of NF-κB, proteasome and DNA topoisomerase. Results: Inhibition of NF-κB transcriptional activity by transient transfection with mutant plasmids encoding Akt1 and glycogen synthase kinase-3β (GSK-3β), or by treatment with chemical inhibitors, wortmannin and LY294002, showed little effect on the survival of Chang/HBx cells. Furthermore, IκBα (S32/36A) mutant plasmid or other NF-κB inhibitors, 1-pyrrolidinecarbonidithioic acid and sulphasalazine, were also shown to have little effect on the cell proliferation. By contrast, proteasome inhibitor-1 (Pro1) and MG132 enhanced the HBx-induced ER-stress response and the subsequent activation of caspase-12, -9 and -3 and reduced cell proliferation. Camptothecin (CPT), however, triggered activation of caspase-3 without induction of caspase-12, and reduced cell proliferation. In addition, CPT-induced cell death was reversed by pre-treatment with z-DEVD, a caspase-3-specific inhibitor. Conclusions: Detailed exploitation of the regulators of caspase-3 activation could open the gate for finding an efficient target for development of anticancer therapeutics against HBx-transformed hepatocellular carcinoma.
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Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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