title: Sigma ligands inhibit the growth of small cell lung cancer cells.
abstract: The effects of sigma ligands on small cell lung cancer (SCLC) cells were investigated. 125I-N-(2-(piperidino)ethyl)-2-iodobenazmide (2-IBP) bound with high affinity to SCLC cell line NCI-H209 and NCI-N417. Specific 125I-2-IBP binding was inhibited with high affinity by ifendipine, haloperidol, (2-piperidinyl-aminoethyl)-4-iodobenzamide (IPAB) and 1,3-ditolylguanidine (DTG) with IC50 values of 3, 10, 15 and 90 nM respectively. In vitro, 10 microM 2-IBP, haloperidol or IPAB inhibited NCI-N417 proliferation using a MTT or clonogenic assay. In vivo, 4 mg/kg IPAB or 2-IBP inhibited NCI-N417 xenograft proliferation. 125I-2-IBP localized to the SCLC tumors after subcutaneous injection. These results suggest that sigma ligands may be utilized to localize and inhibit the proliferation of SCLC tumors.
authors.affiliation: Cell and Cancer Biology Dept. Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Moody
authors.forename: J
authors.initials: J
authors.lastname: Leyton
authors.forename: C
authors.initials: C
authors.lastname: John
mesh_terms: D000818:Animals; D001549:Benzamides / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001667:Binding, Competitive / Q000187:drug effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010880:Piperidines / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017480:Receptors, sigma / Q000378:metabolism / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D001549:Benzamides; D006146:Guanidines; D008024:Ligands; D010880:Piperidines; D017480:Receptors, sigma; C066918:N-(2-(diethylamino)ethyl)-4-iodobenzamide; C084662:4-iodo-N-piperidinoethylbenzamide; D006220:Haloperidol; C050232:1,3-ditolylguanidine