title: Norcantharidin induces cell cycle arrest and inhibits progression of human leukemic Jurkat T cells through mitogen-activated protein kinase-mediated regulation of interleukin-2 production.
abstract: Norcantharidin (NCTD) is a potential anti-cancer agent that inhibits proliferation and induces cell death through regulation of mitogen-activated protein kinases (MAPK). This study examined the effect of NCTD on tumor cells by using a model of phorbol 12-myristate 13-acetate plus ionomycin (PMAI)-activated leukemia Jurkat T cells. The results showed that NCTD significantly inhibited the viability of cells with and without PMAI treatment. NCTD induced cell cycle arrest at G2/M phase, down-regulated the expression of calcineurin and, by itself or in combination with Cyclosporine A, reduced calcineurin phosphatase activity. Furthermore, NCTD up-regulates the expression of phosphorylated (p)-P38 and p-ERK1/2, but not JNK in PMAI-activated Jurkat T cells, in accordance with the alteration in viability. Regarding major cytokine and chemokine secretion profile, NCTD attenuates PMAI-augmented production of IL-2, but slightly increases or has no effect on TNF-α and IL-8. By blockade of various MAPK, NCTD regulates PMAI-augmented IL-2 production through activation of P38 and ERK1/2, in accordance with the aforementioned MAPK expression. In conclusion, NCTD inhibited IL-2 production in PMAI-activated human leukemia Jurkat T cells through activation of P38 and ERK1/2, suggesting that NCTD might have the potential of being used as a chemopreventive agent to inhibit tumor progression in the future.
authors.affiliation: Department of Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Liao
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.forename: Chin-Hung
authors.initials: CH
authors.lastname: Chou
authors.forename: Fang-Wei
authors.initials: FW
authors.lastname: Wang
authors.forename: Cheng-Deng
authors.initials: CD
authors.lastname: Kuo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D019703:Calcineurin / Q000378:metabolism; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C508606:CXCL8 protein, human; D002273:Carcinogens; C508594:IL2 protein, human; D007376:Interleukin-2; D016209:Interleukin-8; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C069741:norcantharidin; C120817:calcineurin phosphatase; D019703:Calcineurin; D010744:Phosphoric Monoester Hydrolases