Influence of mitoxantrone on nucleolar function in MDA-MB-231 human breast tumor cell line.
The effect of mitoxantrone (DHAQ) on [3H]thymidine and [3H]uridine incorporation by exponentially growing MDA-MB-231, a human breast tumor cell line has been studied. The results have indicated that DHAQ was more effective in inhibiting [3H]thymidine than [3H]uridine incorporation in a concentration dependent manner. Following drug treatment at 20 ng/ml concentration, 50% inhibition of growth and [3H]thymidine incorporation were noted, whereas [3H]uridine incorporation was only inhibited by about 12%. At 2000 ng/ml of DHAQ the inhibition of cell growth, [3H]thymidine and [3H]uridine incorporations were 78%, 95% and 62%, respectively. Nuclear-associated radioactivity detected at light and electron microscope autoradiographic levels after [3H]thymidine and [3H]uridine incorporations, into DHAQ treated cells indicated that DHAQ prevented the accumulation of radioactivity into the nuclei in a concentration dependent manner. These results gave further indication that mitoxantrone induced a definitive alteration of nuclear template activities, correlated with nuclear functional-structural relation and suggested that the nucleoli were the primary site of DHAQ action.
Chegini
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Department of Obstetrics & Gynecology, School of Medicine, University of Louisville, KY 40292.
Safa
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AR
D001345:Autoradiography; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects; D002466:Cell Nucleolus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008854:Microscopy, Electron; D008942:Mitoxantrone / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D008942:Mitoxantrone