Anti-cancer effects of thymoquinone in mouse neuroblastoma (Neuro-2a) cells through caspase-3 activation with down-regulation of XIAP

• Published in: Toxicology letters Vol. 213; no. 2; pp. 151 - 159
• Main Authors: Paramasivam, Arumugam, Sambantham, Shanmugam, Shabnam, Jawahar, Raghunandhakumar, Subramanian, Anandan, Balakrishnan, Rajiv, Rose, Vijayashree Priyadharsini, Jayaseelan, Jayaraman, Gopalswamy
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 03.09.2012; Elsevier
• Subjects: Animals; Antineoplastic agents; Apoptosis; Apoptosis - drug effects; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Benzoquinones - pharmacology; Biological and medical sciences; Blotting, Western; Caspase; Caspase 3 - metabolism; Cell Line, Tumor; Chemotherapy; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Enzyme Activation - drug effects; Medical sciences; Membrane Potential, Mitochondrial - drug effects; Mice; Neuroblastoma; Neuroblastoma - drug therapy; Neuroblastoma - enzymology; Neuroblastoma - metabolism; Neurology; Pharmacology. Drug treatments; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - chemistry; RNA, Messenger - genetics; Thymoquinone; Tumors of the nervous system. Phacomatoses; X-Linked Inhibitor of Apoptosis Protein - metabolism; XIAP; Caspase; XIAP; Neuroblastoma; Thymoquinone; Apoptosis; Antineoplastic agent; Nervous system diseases; Enzyme; Cysteine endopeptidases; Rodentia; Malignant tumor; In vitro; X linked inhibitor of apoptosis protein; Peptidases; Vertebrata; Mammalia; Apoptosis inhibitory protein; Mouse; Cell death; Animal; Hydrolases; Autonomic neuropathy; Cancer
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2012.06.011

► TQ was found to exhibit cytotoxicity against mouse neuroblastoma cell line, Neuro-2a. ► Cell viability was inhibited in a dose and time-dependent manner. ► TQ triggered apoptotic pathway as evidenced by increased Bax/Bcl2 ratio and release of cytochrome c from mitochondria. ► TQ activates Caspase-3 followed by the cleavage of PARP. ► XIAP, an inhibitor protein of apoptosis was found to be down regulated in TQ-treated neuroblastoma cells. 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.