title: Downregulation of nucleoporin 88 and 214 induced by oridonin may protect             OCIM2 acute erythroleukemia cells from apoptosis through regulation of nucleocytoplasmic             transport of NF-κB.
abstract: Oridonin has been utilized for the treatment of various human diseases due to its anti-inflammatory, antibacterial and antitumor effects. However, the precise mechanisms induced by oridonin in human erythroleukemia are yet to be clarified. The present study aimed to elucidate possible oridonin-induced apoptotic mechanisms in OCIM2 cells, as well as the possible mechanisms whereby OCIM2 cells are relatively resistant to oridonin. Results in the present study showed that oridonin significantly inhibited OCIM2 and OCI-AML3 cell proliferation in a dose- and time-dependent manner, while expressing a much higher IC50 in OCIM2, compared to OCI-AML3. These results also indicated that oridonin induced OCIM2 cell apoptosis, associated with p65 and Bax, while activating caspases-9, -6 and -3. However, p65 was only partly translocated into the nucleus, while most of the p65 was retained in the cytoplasm. Moreover, nucleoporin 214 (Nup214) and nucleoporin 88 (Nup88) were downregulated at the transcriptional and protein levels, subsequent to oridonin treatment. Taken together, these data suggest that oridonin has the potential to induce OCIM2 cell-apoptosis, involving NF-κB activation, whereas the downregulation of Nup88 and Nup214 may protect OCIM2 through the regulation of the nucleocytoplasmic transport of p65.
authors: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors: Sha
authors: S
authors: Yi
authors: Yan
authors: Y
authors: Chen
authors: Lu
authors: L
authors: Wen
authors: Lijing
authors: L
authors: Yang
authors: Guohui
authors: G
authors: Cui
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D045786:Diterpenes, Kaurane; D016328:NF-kappa B; C085914:NUP214 protein, human; C104835:NUP88 protein, human; D028861:Nuclear Pore Complex Proteins; C011959:oridonin