title: The ability to survive mitosis in the presence of microtubule poisons differs significantly between human nontransformed (RPE-1) and cancer (U2OS, HeLa) cells.
abstract: We used live cell imaging to compare the fate of human nontransformed (RPE-1) and cancer (HeLa, U2OS) cells as they entered mitosis in nocodazole or taxol. In the same field, and in either drug, a cell in all lines could die in mitosis, exit mitosis and die within 10 h, or exit mitosis and survive > or =10 h. Relative to RPE-1 cells, significantly fewer HeLa or U2OS cells survived mitosis or remained viable after mitosis: in nocodazole concentrations that inhibit spindle microtubule assembly, or in 500 nM taxol, 30% and 27% of RPE-1 cells, respectively, died in or within 10 h of exiting mitosis while 90% and 49% of U2OS and 78% and 81% of HeLa died. This was even true for clinically relevant taxol concentrations (5 nM) which killed 93% and 46%, respectively, of HeLa and U2OS cells in mitosis or within 10 h of escaping mitosis, compared to 1% of RPE-1 cells. Together these data imply that studies using HeLa or U2OS cells, harvested after a prolonged block in mitosis with nocodazole or taxol, are significantly contaminated with dead or dying cells. We also found that the relationship between the duration of mitosis and survival is drug and cell type specific and that lethality is related to the cell type and drug used to prevent satisfaction of the kinetochore attachment checkpoint. Finally, work with a pan-caspase inhibitor suggests that the primary apoptotic pathway triggered by nocodazole during mitosis in RPE-1 cells is not active in U2OS cells. Cell Motil. Cytoskeleton 2008. (c) 2008 Wiley-Liss, Inc.
authors.affiliation: Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York, USA.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Brito
authors.forename: Conly L
authors.initials: CL
authors.lastname: Rieder
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008853:Microscopy; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects*; D015739:Nocodazole / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D008941:Spindle Apparatus / Q000187:drug effects; D050257:Tubulin Modulators / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D050257:Tubulin Modulators; D017239:Paclitaxel; D015739:Nocodazole
references.citation: Mol Biol Cell. 2006 Dec;17(12):5227-40
references.pmid: 17035635
references.citation: Cancer Res. 2002 Apr 1;62(7):1935-8
references.pmid: 11929805
references.citation: J Cell Biol. 1994 Nov;127(3):789-802
references.pmid: 7962060
references.citation: J Cell Sci. 1992 Jul;102 ( Pt 3):401-16
references.pmid: 1506423
references.citation: Cancer Res. 2008 May 1;68(9):3269-76
references.pmid: 18451153
references.citation: Cell Cycle. 2005 Oct;4(10):1385-8
references.pmid: 16138009
references.citation: Am J Pathol. 2003 Sep;163(3):1109-16
references.pmid: 12937152
references.citation: Curr Biol. 2006 Jun 20;16(12):1194-200
references.pmid: 16782009
references.citation: Dev Cell. 2004 Nov;7(5):637-51
references.pmid: 15525526
references.citation: Nat Cell Biol. 2008 Jun;10(6):748-51
references.pmid: 18469805
references.citation: Cancer. 2000 Jun 1;88(11):2619-28
references.pmid: 10861441
references.citation: J Cell Biol. 2004 Jun 7;165(5):609-15
references.pmid: 15184397
references.citation: Nat Rev Mol Cell Biol. 2007 May;8(5):379-93
references.pmid: 17426725
references.citation: Cancer Cell. 2005 Jul;8(1):7-12
references.pmid: 16023594
references.citation: Oncogene. 2005 Jun 16;24(26):4301-10
references.pmid: 15782113
references.citation: Methods. 2006 Jan;38(1):2-16
references.pmid: 16343936
references.citation: Cancer Res. 2003 Jun 1;63(11):2794-801
references.pmid: 12782584
references.citation: EMBO Rep. 2001 Jul;2(7):609-14
references.pmid: 11454737
references.citation: Apoptosis. 2006 May;11(5):765-71
references.pmid: 16532268
references.citation: Pharmacol Ther. 1991 Oct;52(1):35-84
references.pmid: 1687171
references.citation: Mol Med. 1995 Jul;1(5):506-26
references.pmid: 8529117
references.citation: Apoptosis. 2003 Aug;8(4):345-52
references.pmid: 12815277
references.citation: Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9552-6
references.pmid: 8105478
references.citation: Cancer Res. 2003 Nov 15;63(22):7891-9
references.pmid: 14633718
references.citation: Apoptosis. 2003 Oct;8(5):413-50
references.pmid: 12975575
references.citation: Curr Cancer Drug Targets. 2007 Dec;7(8):730-42
references.pmid: 18220533
references.citation: Genes Dev. 1996 Oct 15;10(20):2621-31
references.pmid: 8895663
references.citation: Cancer Res. 1998 Oct 15;58(20):4667-72
references.pmid: 9788620
references.citation: J Cell Biol. 2008 Aug 25;182(4):623-9
references.pmid: 18710927
references.citation: Mol Cell Biol. 1998 Feb;18(2):1055-64
references.pmid: 9448003
references.citation: Cold Spring Harb Symp Quant Biol. 1991;56:417-25
references.pmid: 1819503
references.citation: Front Biosci. 2008 Jan 01;13:2103-14
references.pmid: 17981695
references.citation: J Cancer Res Clin Oncol. 1996;122(4):214-8
references.pmid: 8601573
references.citation: Cell. 1991 Aug 9;66(3):507-17
references.pmid: 1651171
references.citation: Mol Cell Biol. 2005 Nov;25(21):9232-48
references.pmid: 16227576
references.citation: Nature. 1998 Mar 19;392(6673):300-3
references.pmid: 9521327
references.citation: Mol Cell. 2007 Apr 27;26(2):301-10
references.pmid: 17466630
references.citation: Chromosoma. 1997 Nov;106(6):348-60
references.pmid: 9362543
references.citation: J Cell Biol. 1994 Dec;127(5):1301-10
references.pmid: 7962091
references.citation: Mol Cell Biol. 2002 Feb;22(3):874-85
references.pmid: 11784863
references.citation: J Cell Biol. 1995 Aug;130(4):941-8
references.pmid: 7642709
references.citation: J Cell Biol. 1996 Nov;135(3):689-700
references.pmid: 8909543
references.citation: Cell. 1991 Aug 9;66(3):519-31
references.pmid: 1651172
references.citation: Nat Genet. 1999 Jan;21(1):111-4
references.pmid: 9916802
references.citation: Nat Rev Cancer. 2004 Apr;4(4):253-65
references.pmid: 15057285
references.citation: Cancer Res. 2004 Apr 1;64(7):2502-8
references.pmid: 15059905
references.citation: Exp Cell Res. 1999 Aug 1;250(2):339-50
references.pmid: 10413588
references.citation: Science. 1995 Mar 3;267(5202):1353-6
references.pmid: 7871434
references.citation: Curr Biol. 2007 Dec 4;17(23):2081-6
references.pmid: 18060787