title: Intracellular distribution of CPT-11 in CPT-11-resistant cells with confocal laser scanning microscopy.
abstract: CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy camptothecin, is a well-known DNA topoisomerase I inhibitor. SN-38 is a metabolite of this compound. Both emit fluorescence when activated by a laser beam. With a confocal laser scanning microscope (CLSM), we determined the intracellular distribution of CPT-11 and SN-38 and the chronological changes in drug-treated PC-7, a cell line of human non-small cell lung cancer, and its CPT-11 resistant variant, PC-7/CPT cells. There were many more granules in the cytoplasm in PC-7/CPT than in the parent cell line (PC-7). The granule formation of the resistant cell could indicate a different drug metabolism in the cytoplasm from that of the parent cell. This technique would provide a new way of investigating the mechanism of resistance of cancer cells to anticancer drugs.
authors.affiliation: Department of Neurosurgery, National Cancer Center Hospital, Tokyo.
authors.forename: H
authors.initials: H
authors.lastname: Oyama
authors.forename: M
authors.initials: M
authors.lastname: Nagane
authors.forename: S
authors.initials: S
authors.lastname: Shibui
authors.forename: K
authors.initials: K
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Mukai
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000648:ultrastructure*; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D007091:Image Processing, Computer-Assisted; D000077146:Irinotecan; D007834:Lasers; D008175:Lung Neoplasms / Q000378:metabolism* / Q000648:ultrastructure*; D008854:Microscopy, Electron; D009685:Nuclear Envelope / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014463:Ultrasonography
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin