Effects of the polyacetylene capillin on human tumour cell lines.
We investigated the effects of capillin, a constituent of Artemisia monosperma, on four human tumour cell lines: colon carcinoma H729, pancreatic carcinoma MIA PaCa-2, epidermoid carcinoma of the larynx HEp-2 and lung carcinoma A549. Cells were treated with capillin to examine both the anti-proliferative and pro-apoptotic effects, as well as the molecular mechanism underlying these effects. Changes in cell proliferation, membrane permeability, macromolecular synthesis, glutathione (GSH), cell cycle and programmed cell death were evaluated. Capillin (1microM-10microM) inhibited cell proliferation and decreased macromolecular synthesis simultaneously, in a dose- and time-dependent manner. Co-incubation with L-buthionine sulfoximine (L-BSO) augmented the efficacy of capillin. Capillin modulated GSH levels, accumulated cells in the S+G2/M-phase of the cell cycle and induced cell death and DNA fragmentation, as indicated by flow cytometry, fluorescence microscopy and DNA fragmentation assay. These findings suggest that capillin has cytotoxic activity and can induce apoptosis in human tumour cell lines.
Whelan
L C
LC
Department of Zoology, University College Dublin, Belfield, Dublin 4, Ireland.
Ryan
M F
MF
D000480:Alkynes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053280:Diynes; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000480:Alkynes; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D053280:Diynes; D009363:Neoplasm Proteins; D010936:Plant Extracts; D012334:RNA, Neoplasm; C065814:capillin; D019328:Buthionine Sulfoximine; D005978:Glutathione