AIM:Mitotic cell death has been focused on in tumor therapy.However,the precise mechanisms underlying it remainunclear.We have reported previously that enediyneantibiotic lidamycin induces mitotic cell death at lowconcentrations in human epithelial tumor cells.The aim ofthis study was to investigate the possible link betweencentrosome dynamics and lidamycin-induced mitotic celldeath in human hepatorna BEL-7402 cells.METHODS:Growth curve was established by MTT assay.Cell multinucleation was detected by staining with Hoechst33342.Flow cytometry was used to analyze cell cycle.Aberrant centrosomes were detected by indirectimmunofluorescence.Western blot and senescence-associated β-galactosidase (SA-β-gal) staining were usedto analyze protein expression and senescence-like phenotype,respectively.RESULTS:Exposure of BEL-7402 cells to a low concentrationof lidamycin resulted in an increase in cells containing multiplecentrosomes in association with the appearance ofmitotic cell death and activation of SA-β-gal in somecells,accompanied by the changes of protein expressionfor the regulation of proliferation and apoptosis.Themitochondrial signaling pathway,one of the major apoptoticpathways,was not activated during mitotic cell death.Theaberrant centrosomes contributed to the multipolar mitoticspindles formation,which might lead to an unbalanceddivision of chromosomes and mitotic cell death characterizedby the manifestation of multi- or micronucleated giant cells.Cell cycle analysis revealed that the lidamycin treatmentprovoked the retardation at G2/M phase,which might beinvolved in the centrosome overduplication.CONCLUSION:Mitotic cell death and senescence canbe induced by treatment of BEL-7402 cells with a lowconcentration of lidamycin.Centrosome dysregulation mayplay a critical role in mitotic failure and ultimate cell deathfollowing exposure to intermediate dose of lidamycin. AIM: Mitotic cell death has been focused on in tumor therapy. Host, the exact mechanisms underlying it remainunclear. We have reported previously that enediyneantibiotic lidamycin induces mitotic cell death at lowconcentrations in human epithelial tumor cells. Aims of this study was to investigate the possible link between centrosome dynamics and lidamycin-induced mitotic celldeath in human hepatorna BEL-7402 cells. METHODS: Growth curve was established by MTT assay. Cell multinucleation was detected by staining with Hoechst 33342. Flow cytometry was used to analyze cell cycle. Aberrant centrosomes were detected by Indirectimmunofluorescence. Western blot and senescence-associated β-galactosidase (SA-β-gal) staining were used to analyze protein expression and senescence-like phenotype, respectively .RESULTS: Exposure of BEL-7402 cells to a low concentration of lidamycin resulted in an increase in cells containing multiplecentrosomes in association with the appearance ofmitotic cell death and ac tivation of SA-β-gal in some cells, accompanied by the changes of protein expression for the regulation of proliferation and apoptosis. The mitochondrial signaling pathway, one of the major apoptotic pathways, was not activated during mitotic cell death. The enzyme centrosomes contribute to the multipolar mitotics pindles formation , which might lead to an unbalanceddivision of chromosomes and mitotic cell death characterized by the manifestation of multi- or micronucleated giant cells. Cell cycle analysis revealed that the lidamycin treatmentprovoked the retardation at G2 / Mphase, which might be in viral in the centrosome overdulication. CONCLUSION: Mitotic cell death and senescence canbe induced by treatment of BEL-7402 cells with a low profile of lidamycin. Centrosome dysregulation may play a critical role in mitotic failure and ultimate cell deathfollowing exposure to intermediate dose of lidamycin.