title: Naftopidil is useful for the treatment of malignant pleural mesothelioma.
abstract: Naftopidil, an α1-adrenoceptor blocker, induced apoptosis of human malignant pleural mesothelioma NCI-H2052 cells. Naftopidil upregulated the expression of tumor necrosis factor-α (TNF-α) mRNA in these cells. Naftopidil, alternatively, increased FasL secretion from NCI-H2052 cells, without affecting the expression of FasL mRNA and protein, and activated caspase-3 and -8 in NCI-H2052 cells. Naftopidil drastically suppressed tumor growth in mice inoculated with these cells. The results of the present study indicate that naftopidil induces apoptosis of NCI-H2052 cells by upregulating the expression of TNF-α and stimulating the secretion of FasL, a ligand for the death receptor Fas, both to activate caspase-8 and the effector caspase-3, leading to the suppression of NCI-H2052 cell proliferation in vivo. This raises the possibility that naftopidil could be developed as an effective drug for the treatment of malignant pleural mesothelioma.
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Mikami
authors.forename: Hisao
authors.initials: H
authors.lastname: Nagaya
authors.forename: Akinobu
authors.initials: A
authors.lastname: Gotoh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanno
authors.forename: Ayako
authors.initials: A
authors.lastname: Tsuchiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishizaki
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008819:Mice, Nude; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000317:Adrenergic alpha-Antagonists; D000970:Antineoplastic Agents; D053222:Fas Ligand Protein; D009281:Naphthalenes; D010879:Piperazines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; C064357:naftopidil