title: In Vitro Anti-Neuroblastoma Activity of Thymoquinone Against Neuro-2a Cells via Cell-cycle Arrest.
abstract: We have recently shown that thymoquinone (TQ) has a potent cytotoxic effect and induces apoptosis via caspase-3 activation with down-regulation of XIAP in mouse neuroblastoma (Neuro-2a) cells. Interestingly, our results showed that TQ was significantly more cytotoxic towards Neuro-2a cells when compared with primary normal neuronal cells. In this study, the effects of TQ on cell-cycle regulation and the mechanisms that contribute to this effect were investigated using Neuro-2a cells. Cell-cycle analysis performed by flow cytometry revealed cell-cycle arrest at G2/M phase and a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Moreover, TQ increased the expression of p53, p21 mRNA and protein levels, whereas it decreased the protein expression of PCNA, cyclin B1 and Cdc2 in a dose- dependent manner. Our finding suggests that TQ could suppress cell growth and cell survival via arresting the cell-cycle in the G2/M phase and inducing apoptosis of neuroblastoma cells.
authors.affiliation: Department of Genetics, Dr.ALM Post Graduate Institute of Basic Medical Sciences, Sekkizhar Campus, University of Madras, Taramani, India E-mail : paramasivam0103@gmail.com.
authors.forename: Arumugam
authors.initials: A
authors.lastname: Paramasivam
authors.forename: Subramanian
authors.initials: S
authors.lastname: Raghunandhakumar
authors.forename: Jayaseelan Vijayashree
authors.initials: JV
authors.lastname: Priyadharsini
authors.forename: Gopalswamy
authors.initials: G
authors.lastname: Jayaraman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D015153:Blotting, Western; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D016227:Benzoquinones; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D020169:Caspases; C003466:thymoquinone