Anti-cancer effects of thymoquinone in mouse neuroblastoma (Neuro-2a) cells through caspase-3 activation with down-regulation of XIAP.
Thymoquinone (TQ) is a bioactive component derived from the medicinal plant Nigella sativa. Recent studies reported that TQ exhibited cytotoxic effects in several cancer cell lines. Currently, no information in the literature is found concerning its mechanisms and cytotoxicity on neuroblastoma cells. In this study, the cytotoxicity of TQ in mouse neuroblastoma cells (Neuro-2a) was investigated. Our results showed that TQ significantly reduced viability of Neuro-2a cells than normal neuronal cells. Apoptosis induction by TQ was confirmed by DAPI and AO/PI staining. TQ triggered the apoptotic pathway, which was characterized by increased Bax/Bcl-2 ratio. TQ significantly increased the expression of pro-apoptotic protein Bax, whereas decreased the expression of anti-apoptotic protein Bcl-2, which leads to the release of cytochrome c from mitochondria into the cytoplasm. Moreover, TQ treatment directs the activation of caspase-3 followed by the cleavage of poly(ADP-ribose) polymerase (PARP). Interestingly, we also observed that TQ down-regulated caspase inhibitor X-linked inhibitor of apoptosis protein (XIAP). These results indicate that TQ induces apoptosis via caspase-3 activation with down-regulation of XIAP in Neuro-2a cells.
Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Sekkizhar Campus, Taramani, Chennai 600113, India.
Arumugam
A
Paramasivam
Shanmugam
S
Sambantham
Jawahar
J
Shabnam
Subramanian
S
Raghunandhakumar
Balakrishnan
B
Anandan
Rose
R
Rajiv
Jayaseelan
J
Vijayashree Priyadharsini
Gopalswamy
G
Jayaraman
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D016227:Benzoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051636:X-Linked Inhibitor of Apoptosis Protein; D051028:bcl-2-Associated X Protein; C505409:Casp3 protein, mouse; D053148:Caspase 3; C003466:thymoquinone