Abstract

The definition of mitotic catastrophe has been the subject of scientific discussion for over a decade. Initially, it was thought that mitotic catastrophe is one of the types of cell death occurring during aberrant mitosis. A number of studies carried out in recent years allowed for a better understanding of the function of this process. According to the definition proposed by the Nomenclature Committee on Cell Death in 2018, mitotic catastrophe is an oncosuppressive mechanism that inhibits the proliferation and/or survival of cells that are unable to complete mitosis by inducing cell death or initiating cellular senescence. Mitotic catastrophe is recognized based on unique nuclear changes, the presence of abnormal mitotic figures and several molecular alterations. It is believed that avoiding mitotic catastrophe by genetically unstable cells promotes their unlimited growth, which can lead to cancer transformation. Therefore, the induction of mitotic catastrophe seems to be a promising strategy for the prevention and treatment of cancer. However, despite the significant role of this process, the molecular events between aberrant mitosis and cell death are still not well understood. It can be assumed that a thorough understanding of signaling pathways linking mitotic catastrophe with cell death will enable the effective use of known inducers of mitotic catastrophe in the treatment of cancer and provide new therapeutic targets. The aim of this review is to present a morphological and functional definition of mitotic catastrophe and its potential role in anticancer therapy.

References

• 1. Ayscough K., Hayles J., MacNeill S.A., Nurse P.: Cold-sensitivemutants of p34cdc2 that suppress a mitotic catastrophe phenotypein fission yeast. Mol. Gen. Genet., 1992; 232: 344–350
  Google Scholar
• 2. Baldwin E.L., Osheroff N.: Etoposide, topoisomerase II and cancer.Curr. Med. Chem. Anticancer Agents, 2005; 5: 363–372
  Google Scholar
• 3. Barnum K.J., O’Connell M.J.: Cell cycle regulation by checkpoints.Methods Mol. Biol., 2014; 1170: 29–40
  Google Scholar
• 4. Bekier M.E., Fischbach R., Lee J., Taylor W.R.: Length of mitotic arrestinduced by microtubule-stabilizing drugs determines cell deathafter mitotic exit. Mol. Cancer Ther., 2009; 8: 1646–1654
  Google Scholar
• 5. Berndtsson M., Konishi Y., Bonni A., Hägg M., Shoshan M., LinderS., Havelka A.M.: Phosphorylation of BAD at Ser-128 during mitosisand paclitaxel-induced apoptosis. FEBS Lett., 2005; 579: 3090–3094
  Google Scholar
• 6. Brito D.A., Rieder C.L.: Mitotic checkpoint slippage in humansoccurs via cyclin B destruction in the presence of an active checkpoint.Curr. Biol., 2006; 16: 1194–1200
  Google Scholar
• 7. Bucher N., Britten C.D.: G2 checkpoint abrogation and checkpointkinase-1 targeting in the treatment of cancer. Br. J. Cancer,2008; 98: 523–528
  Google Scholar
• 8. Cao Y.N., Zheng L.L., Wang D., Liang X.X., Gao F., Zhou X.L.: Recentadvances in microtubule-stabilizing agents. Eur. J. Med. Chem.,2018; 143: 806–828
  Google Scholar
• 9. Castedo M., Coquelle A., Vivet S., Vitale I., Kauffmann A., DessenP., Pequignot M.O., Casares N., Valent A., Mouhamad S., SchmittE., Modjtahedi N., Vainchenker W., Zitvogel L., Lazar V., Garrido C.,Kroemer G.: Apoptosis regulation in tetraploid cancer cells. EMBOJ., 2006; 25: 2584–2595
  Google Scholar
• 10. Castedo M., Perfettini J.L., Roumier T., Andreau K., MedemaR., Kroemer G.: Cell death by mitotic catastrophe: a moleculardefinition. Oncogene, 2004; 23: 2825–2837
  Google Scholar
• 11. Castedo M., Perfettini J.L., Roumier T., Kroemer G.: Cyclin-dependentkinase-1: linking apoptosis to cell cycle and mitotic catastrophe.Cell Death Differ., 2002; 9: 1287–1293
  Google Scholar
• 12. Castedo M., Perfettini J.L., Roumier T., Valent A., Raslova H.,Yakushijin K., Horne D., Feunteun J., Lenoir G., Medema R., VainchenkerW., Kroemer G.: Mitotic catastrophe constitutes a special caseof apoptosis whose suppression entails aneuploidy. Oncogene, 2004;23: 4362–4370
  Google Scholar
• 13. Cenklová V.: Photodynamic therapy with TMPyP – Porphyrineinduces mitotic catastrophe and microtubule disorganization inHeLa and G361 cells, a comprehensive view of the action of the photosensitizer.J. Photochem. Photobiol. B, 2017; 173: 522–537
  Google Scholar
• 14. Chang B.D., Broude E.V., Dokmanovic M., Zhu H., Ruth A., XuanY., Kandel E.S., Lausch E., Christov K., Roninson I.B.: A senescencelikephenotype distinguishes tumor cells that undergo terminalproliferation arrest after exposure to anticancer agents. CancerRes., 1999; 59: 3761–3767
  Google Scholar
• 15. Choi M., Kim W., Cheon M.G., Lee C.W., Kim J.E.: Polo-like kinase 1 inhibitor BI2536 causes mitotic catastrophe following activationof the spindle assembly checkpoint in non-small cell lung cancercells. Cancer Lett., 2015; 357: 591–601
  Google Scholar
• 16. Dawar S., Lim Y., Puccini J., White M., Thomas P., Bouchier-HayesL., Green D.R., Dorstyn L., Kumar S.: Caspase-2-mediated cell death isrequired for deleting aneuploid cells. Oncogene, 2017; 36: 2704–2714
  Google Scholar
• 17. De Witt Hamer P.C., Mir S.E., Noske D., Van Noorden C.J.,Würdinger T.: WEE1 kinase targeting combined with DNA-damagingcancer therapy catalyzes mitotic catastrophe. Clin. Cancer Res.,2011; 17: 4200–4207
  Google Scholar
• 18. Denisenko T.V., Sorokina I.V., Gogvadze V., Zhivotovsky B.: Mitoticcatastrophe and cancer drug resistance: A link that must to bebroken. Drug Resist. Updat., 2016; 24: 1–12
  Google Scholar
• 19. Do K., Doroshow J.H., Kummar S.: Wee1 kinase as a target forcancer therapy. Cell Cycle, 2013; 12: 3159–3164
  Google Scholar
• 20. Dominguez-Brauer C., Thu K.L., Mason J.M., Blaser H., Bray M.R.,Mak T.W.: Targeting mitosis in cancer: Emerging strategies. Mol.Cell, 2015; 60: 524–536
  Google Scholar
• 21. Eom Y.W., Kim M.A., Park S.S., Goo M.J., Kwon H.J., Sohn S., KimW.H., Yoon G., Choi K.S.: Two distinct modes of cell death inducedby doxorubicin: apoptosis and cell death through mitotic catastropheaccompanied by senescence-like phenotype. Oncogene, 2005;24: 4765–4777
  Google Scholar
• 22. Fava L.L., Schuler F., SladkyV., Haschka M.D., Soratroi C., EitererL., Demetz E., Weiss G., Geley S., Nigg E.A., Villunger A.: The PIDDosomeactivates p53 in response to supernumerary centrosomes.Genes Dev., 2017; 31: 34–45
  Google Scholar
• 23. Furth N., Aylon Y.: The LATS1 and LATS2 tumor suppressors:beyond the Hippo pathway. Cell Death Differ., 2017; 24: 1488–1501
  Google Scholar
• 24. Galluzzi L., Maiuri M.C., Vitale I., Zischka H., Castedo M., ZitvogelL., Kroemer G.: Cell death modalities: classification and pathophysiologicalimplications. Cell Death Differ., 2007; 14: 1237–1243
  Google Scholar
• 25. Galluzzi L., Vitale I., Aaronson S.A., Abrams J.M., Adam D., AgostinisP., Alnemri E.S., Altucci L., Amelio I., Andrews D.W., Annicchiarico-Petruzzelli M., Antonov A.V., Arama E., Baehrecke E.H., BarlevN.A. i wsp.: Molecular mechanisms of cell death: recommendationsof the Nomenclature Committee on Cell Death 2018. Cell Death Differ.,2018; 25: 486–541
  Google Scholar
• 26. Ganem N.J., Cornils H., Chiu S.Y., O’Rourke K.P., Arnaud J., YimlamaiD., Théry M., Camargo F.D., Pellman D.: Cytokinesis failure triggershippo tumor suppressor pathway activation. Cell, 2014; 158:833–848
  Google Scholar
• 27. Gascoigne K.E., Taylor S.S.: Cancer cells display profound intraandinterlinevariation following prolonged exposure to antimitoticdrugs. Cancer Cell, 2008; 14: 111–122
  Google Scholar
• 28. Gerecitano J.F., Stephenson J.J., Lewis N.L., Osmukhina A., Li J.,Wu K., You Z., Huszar D., Skolnik J.M., Schwartz G.K.: A phase I trialof the kinesin spindle protein (Eg5) inhibitor AZD4877 in patientswith solid and lymphoid malignancies. Invest. New Drugs, 2013;31: 355–362
  Google Scholar
• 29. Gu J., Kaufman G., Mavis C., Czuczman M., Hernandez-IlizaliturriF.: Mitotic catastrophe and cell cycle arrest are alternative cell deathpathways executed by bortezomib in rituximab resistant B-cell lymphomacells. Oncotarget, 2017; 8: 12741–12753
  Google Scholar
• 30. Hao Z., Kota V.: Volasertib for AML: clinical use and patient consideration.Onco Targets Ther., 2015; 8: 1761–1771
  Google Scholar
• 31. Harding S.M., Benci J.L., Irianto J., Discher D.E., Minn A.J., GreenbergR.A.: Mitotic progression following DNA damage enables patternrecognition within micronuclei. Nature, 2017; 548: 466–470
  Google Scholar
• 32. Hashimoto O., Shinkawa M., Torimura T., Nakamura T., SelvendiranK., Sakamoto M., Koga H., Ueno T., Sata M.: Cell cycle regulationby the Wee1 inhibitor PD0166285, pyrido [2,3-d] pyimidine, in theB16 mouse melanoma cell line. BMC Cancer, 2006; 6: 292
  Google Scholar
• 33. Huertas D., Soler M., Moreto J., Villanueva A., Martinez A., Vidal A.,Charlton M., Moffat D., Patel S., McDermott J., Owen J., Brotherton D.,Krige D., Cuthill S., Esteller M.: Antitumor activity of a small-moleculeinhibitor of the histone kinase Haspin. Oncogene, 2012; 31: 1408–1418
  Google Scholar
• 34. Innocente S.A., Abrahamson J.L., Cogswell J.P., Lee J.M.: p53regulates a G2 checkpoint through cyclin B1. Proc. Natl. Acad. Sci.USA, 1999; 96: 2147–2152
  Google Scholar
• 35. Kawabe T.: G2 checkpoint abrogators as anticancer drugs. Mol.Cancer Ther., 2004; 3: 513–519
  Google Scholar
• 36. Klimaszewska-Wisniewska A., Halas-Wisniewska M., TadrowskiT., Gagat M., Grzanka D., Grzanka A.: Paclitaxel and the dietaryflavonoid fisetin: a synergistic combination that induces mitoticcatastrophe and autophagic cell death in A549 non-small cell lungcancer cells. Cancer Cell. Int., 2016; 16: 10
  Google Scholar
• 37. Konishi Y., Lehtinen M., Donovan N., Bonni A.: Cdc2 phosphorylationof BAD links the cell cycle to the cell death machinery. Mol.Cell, 2002; 9: 1005–1016
  Google Scholar
• 38. Kroemer G., Galluzzi L., Vandenabeele P., Abrams J., Alnemri E.S.,Baehrecke E.H., Blagosklonny M.V., El-Deiry W.S., Golstein P., GreenD.R., Hengartner M., Knight R.A., Kumar S., Lipton S.A., Malorni W.i wsp.: Classification of cell death: recommendations of the NomenclatureCommittee on Cell Death 2009. Cell Death Differ., 2009; 16: 3–11
  Google Scholar
• 39. Kubara P.M., Kernéis-Golsteyn S., Studény A., Lanser B.B., MeijerL., Golsteyn R.M.: Human cells enter mitosis with damaged DNAafter treatment with pharmacological concentrations of genotoxicagents. Biochem. J., 2012; 446: 373–381
  Google Scholar
• 40. Lara-Gonzalez P., Westhorpe F.G., Taylor S.S.: The spindle assemblycheckpoint. Curr. Biol., 2012; 22: 966–980
  Google Scholar
• 41. Lee J.W., Parameswaran J., Sandoval-Schaefer T., Eoh K.J., YangD.H., Zhu F., Mehra R., Sharma R., Gaffney S.G., Perry E.B., TownsendJ.P., Serebriiskii I.G., Golemis E.A., Issaeva N., Yarbrough W.G., Koo J.S.,Burtness B.: Combined Aurora kinase A (AURKA) and WEE1 inhibitiondemonstrates synergistic antitumor effect in squamous cell carcinomaof the head and neck. Clin. Cancer Res., 2019; 25: 3430–3442
  Google Scholar
• 42. Li J., Hong M.J., Chow J.P., Man W.Y., Mak J.P., Ma H.T., Poon R.Y.:Co-inhibition of polo-like kinase 1 and Aurora kinases promotes mitoticcatastrophe. Oncotarget, 2015; 6: 9327–9340
  Google Scholar
• 43. Li T., Chen Z.J.: The cGAS-cGAMP-STING pathway connects DNAdamage to inflammation, senescence, and cancer. J. Exp. Med., 2018;215: 1287–1299
  Google Scholar
• 44. Li Y., Seto E.: HDACs and HDAC inhibitors in cancer developmentand therapy. Cold Spring Harb. Perspect. Med., 2016; 6: a026831
  Google Scholar
• 45. Liu H., Zhang H., Wu X., Ma D., Wu J., Wang L., Jiang Y., Fei Y.,Zhu C., Tan R., Jungblut P., Pei G., Dorhoi A., Yan Q., Zhang F. i wsp.:Nuclear cGAS suppresses DNA repair and promotes tumorigenesis.Nature, 2018; 563: 131–136
  Google Scholar
• 46. Lock R.B., Stribinskiene L.: Dual modes of death induced by etoposidein human epithelial tumor cells allow Bcl-2 to inhibit apoptosiswithout affecting clonogenic survival. Cancer Res., 1996; 56: 4006–4012
  Google Scholar
• 47. López-García C., Sansregret L., Domingo E., McGranahan N., HoborS., Birkbak N.J., Horswell S., Grönroos E., Favero F., Rowan A.J.,Matthews N., Begum S., Phillimore B., Burrell R., Oukrif D. i wsp.:BCL9L dysfunction impairs caspase-2 expression permitting aneuploidytolerance in colorectal cancer. Cancer Cell, 2017; 31: 79–93
  Google Scholar
• 48. Mackenzie K.J., Carroll P., Martin C.A., Murina O., Fluteau A.,Simpson D.J., Olova N., Sutcliffe H., Rainger J.K., Leitch A., OsbornR.T., Wheeler A.P., Nowotny M., Gilbert N., Chandra T., Reijns M.A.,Jackson A.P.: cGAS surveillance of micronuclei links genome instabilityto innate immunity. Nature, 2017; 548: 461–465
  Google Scholar
• 49. Malumbres M., Pérez de Castro I.: Aurora kinase A inhibitors:promising agents in antitumoral therapy. Expert Opin. Ther. Targets,2014; 18: 1377–1393
  Google Scholar
• 50. Mascaraque M., Delgado-Wicke P., Alejandra D., Lucena S.,Carrasco E., Juarranz A.: Mitotic catastrophe induced in HeLa tumorcells by photodynamic therapy with methyl-aminolevulinate.Int. J. Mol. Sci. 2019; 20: 1229
  Google Scholar
• 51. Mc Gee M.M.: Targeting the mitotic catastrophe signaling pathwayin cancer. Mediators Inflamm., 2015; 2015: 146282
  Google Scholar
• 52. Meulenbeld H.J., Mathijssen R.H., Verweij J., de Wit R., de JongeM.J.: Danusertib, an aurora kinase inhibitor. Expert Opin. Investig.Drugs, 2012; 21: 383–393
  Google Scholar
• 53. Min Y.H., Kim W., Kim J.: The Aurora kinase A inhibitor TC-A2317disrupts mitotic progression and inhibits cancer cell proliferation.Oncotarget, 2016; 7: 84718–84735
  Google Scholar
• 54. Molz L., Booher R., Young P., Beach D.: cdc2 and the regulationof mitosis: six interacting mcs genes. Genetics, 1989; 122: 773–782
  Google Scholar
• 55. Navarro-Serer B., Childers E.P., Hermance N.M., Mercadante D.,Manning A.L.: Aurora A inhibition limits centrosome clustering andpromotes mitotic catastrophe in cells with supernumerary centrosomes.Oncotarget, 2019; 10: 1649–1659
  Google Scholar
• 56. Neelsen K.J., Zanini I.M., Herrador R., Lopes M.: Oncogenes inducegenotoxic stress by mitotic processing of unusual replicationintermediates. J. Cell Biol., 2013; 200: 699–708
  Google Scholar
• 57. Nitta M., Kobayashi O., Honda S., Hirota T., Kuninaka S., MarumotoT., Ushio Y., Saya H.: Spindle checkpoint function is requiredfor mitotic catastrophe induced by DNA-damaging agents. Oncogene,2004; 23: 6548–6558
  Google Scholar
• 58. Rello-Varona S., Kepp O., Vitale I., Michaud M., Senovilla L., JemaàM., Joza N., Galluzzi L., Castedo M., Kroemer G.: An automatedfluorescence videomicroscopy assay for the detection of mitoticcatastrophe. Cell Death Dis., 2010; 1: e25
  Google Scholar
• 59. Roninson I.B., Broude E.V., Chang B.D.: If not apoptosis, thenwhat? Treatment-induced senescence and mitotic catastrophe intumor cells. Drug Resist. Updat., 2001; 4: 303–313
  Google Scholar
• 60. Ruth A.C., Roninson I.B.: Effects of the multidrug transporterP-glycoprotein on cellular responses to ionizing radiation. CancerRes., 2000; 60: 2576–2578
  Google Scholar
• 61. Shah J.J., Kaufman J.L., Zonder J.A., Cohen A.D., BensingerW.I., Hilder B.W., Rush S.A., Walker D.H., Tunquist B.J., LitwilerK.S., Ptaszynski M., Orlowski R.Z., Lonial S.: A phase 1 and 2 studyof Filanesib alone and in combination with low-dose dexamethasonein relapsed/refractory multiple myeloma. Cancer, 2017;123: 4617–4630
  Google Scholar
• 62. Sorokina I.V., Denisenko T.V., Imreh G., Tyurin-Kuzmin P.A., KaminskyyV.O., Gogvadze V., Zhivotovsky B.: Involvement of autophagyin the outcome of mitotic catastrophe. Sci. Rep., 2017; 7: 14571
  Google Scholar
• 63. Tangutur A.D., Kumar D., Krishna K.V., Kantevari S.: Microtubuletargeting agents as cancer chemotherapeutics: An overview ofmolecular hybrids as stabilizing and destabilizing agents. Curr. Top.Med. Chem., 2017; 17: 2523–2537
  Google Scholar
• 64. Theoclitou M.E., Aquila B., Block M.H., Brassil P.J., Castriotta L.,Code E., Collins M.P., Davies A.M., Deegan T., Ezhuthachan J., Filla S.,Freed E., Hu H., Huszar D., Jayaraman M. i wsp.: Discovery of (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877),a kinesin spindle protein inhibitor and potential anticancer agent.J. Med. Chem., 2011; 54: 6734–6750
  Google Scholar
• 65. Thompson S.L., Compton D.A.: Proliferation of aneuploid humancells is limited by a p53-dependent mechanism. J. Cell Biol.,2010; 188: 369–381
  Google Scholar
• 66. Tischer J., Gergely F.: Anti-mitotic therapies in cancer. J. CellBiol., 2019; 218: 10–11
  Google Scholar
• 67. Vakifahmetoglu H., Olsson M., Zhivotovsky B.: Death througha tragedy: mitotic catastrophe. Cell Death Differ., 2008; 15: 1153–1162
  Google Scholar
• 68. Vitale I., Galluzzi L., Castedo M., Kroemer G.: Mitotic catastrophe:a mechanism for avoiding of genomic instability. Nat. Rev. Mol.Cell Biol., 2011; 12: 385–392
  Google Scholar
• 69. Vitale I., Galluzzi L., Vivet S., Nanty L., Dessen P., Senovilla L.,Olaussen K.A., Lazar V., Prudhomme M., Golsteyn R.M., Castedo M.,Kroemer G.: Inhibition of Chk1 kills tetraploid tumor cells througha p53-dependent pathway. PLoS One, 2007; 2: e1337
  Google Scholar
• 70. Vitale I., Manic G., Castedo M., Kroemer G.: Caspase 2 in mitoticcatastrophe: The terminator of aneuploid and tetraploid cells. Mol.Cell. Oncol., 2017; 4: e1299274
  Google Scholar
• 71. Vitale I., Senovilla L., Jemaà M., Michaud M., Galluzzi L., KeppO., Nanty L., Criollo A., Rello-Varona S., Manic G., Métivier D., VivetS., Tajeddine N., Joza N., Valent A., Castedo M., Kroemer G.: Multipolarmitosis of tetraploid cells: inhibition by p53 and dependencyon Mos. EMBO J., 2010; 29: 1272–1284
  Google Scholar
• 72. Yan M., Wang C., He B., Yang M., Tong M., Long Z., Liu B., PengF., Xu L., Zhang Y., Liang D., Lei H., Subrata S., Kelley K.W., Lam E.W.,Jin B., Liu Q.: Aurora-A kinase: A potent oncogene and target forcancer therapy. Med. Res. Rev., 2016; 36: 1036–1079
  Google Scholar
• 73. Zeng X., Sigoillot F., Gaur S., Choi S., Pfaff K.L., Oh D.C., Hathaway N.,Dimova N., Cuny G.D., King R.W.: Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitoticarrest in the absence of spindle damage. Cancer Cell, 2010; 18: 382–395
  Google Scholar

Full text