NTBN, a free radical spin trap induces programmed cell death in human pancreatic cancer (PANC-1) cells.
N-tertiary butyl-a-phenylnitrone, a free radical spin trap at > or = 10 mM concentration, inhibited proliferation and reduced the viability of human pancreatic cancer (Panc-1) cells. The drug concentration determined the extent of inhibition, and with continued culture a proportion of the cells detached, most of which stained with trypan blue. Although hypodiploid cells were detected by flow cytometry of cells cultured with 20 mM NTBN, DNA laddering was absent and the TUNEL reaction negative. "Dark" cells present in samples cultured with 10 mM NTBN exhibited decreased cytoplasmic volume and increased staining with methylene blue and azure II, but lacked characteristic nuclear changes of type 1 programmed cell death. Cells cultured with > 10 mM of the spin trap exhibited nuclear and cytoplasmic changes more consistent with a non-type 1, type 2 variant of PCD with extensive cytoplasmic vacuolization. Careful analysis revealed evidence of marked pinocytosis in some cells. In view of the spin-trap associated pinocytosis, augmented uptake of chemotherapy in affected cells might be anticipated, but additive, synergistic or antagonistic interactions between NTBN and 5-fluorouracil were not observed.
Anderson
K M
KM
Department of Medicine, Rush Medical College, Chicago, Il. 60612, USA. Kanderso@Rush.Edu
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Alrefai
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Harris
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D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D003497:Cyclic N-Oxides; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D009589:Nitrogen Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000473:pathology; D013113:Spin Labels; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D003497:Cyclic N-Oxides; D004273:DNA, Neoplasm; D009589:Nitrogen Oxides; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone; D005472:Fluorouracil