title: Vincristine induces cell cycle arrest and apoptosis in SH-SY5Y human             neuroblastoma cells.
abstract: Neuroblastoma is a common childhood tumor. Vincristine (VCR), an alkaloid             extracted from Catharanthus roseus, is commonly used in combination chemotherapy.             However, the mechanisms of VCR-induced neuroblastoma cell death are not clear.             The aim of this study was to investigate the impact of VCR on mitosis and apoptosis             of SH-SY5Y neuroblastoma cells and the underlying mechanisms. SH-SY5Y cells were             treated with increasing VCR doses for different time points. Cell proliferation             was detected using the MTT assay. Mitotic rate was quantified by immunofluorescence.             Cell cycle and apoptosis were analyzed by flow cytometry. The mRNA and protein             expression of caspase-3 and -9 (apoptotic factors), as well as cyclin B and D             (cell cycle factors), was evaluated by real-time (RT)-PCR and western blot analysis,             respectively. VCR inhibited SH-SY5Y cell proliferation in a time- and dose-dependent             manner (P<0.05). The IC50 of VCR in SH-SY5Y cells was determined as 0.1 µM.             VCR at 0.1 µM induced mitotic arrest and apoptosis, promoted the expression of             caspase-3 and -9 and cyclin B, while decreasing the expression of cyclin D at             6, 12, 18 and 24 h. Except for the mRNA expression of cyclin D at 6 h, these changes             were significant at both the mRNA and protein levels (P<0.05). VCR induces             mitotic arrest of SH-SY5Y cells by regulating cyclin B and D. It further induces             apoptosis in these cells through the activation of caspase-3 and -9. This study             provides fundamental evidence for the application of VCR in neuroblastoma chemotherapy.
authors.affiliation: Institute of Traumatic Brain Injury and Neurological Diseases, Center for Neurology and Neurosurgery, Pingjin Hospital, Tianjin 300162, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tu
authors.forename: Shixiang
authors.initials: S
authors.lastname: Cheng
authors.forename: Sai
authors.initials: S
authors.lastname: Zhang
authors.forename: Hongtao
authors.initials: H
authors.lastname: Sun
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014750:Vincristine / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; C530104:CCND1 protein, human; D056744:Cyclin B1; D012333:RNA, Messenger; D019938:Cyclin D1; D014750:Vincristine; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9