Myristicin-induced neurotoxicity in human neuroblastoma SK-N-SH cells.
Myristicin, 1-allyl-3,4-methylenedioxy-5-methoxybenzene, is a naturally occurring alkenylbenzene compound found in the nutmeg. The present study was conducted to assess the cytotoxic and apoptotic effects of myristicin on the human neuroblastoma SK-N-SH cells. We found that a dose-dependent reduction in cell viability occurs at myristicin concentration > or =0.5 mM in SK-N-SH cells. Apoptotic cell death was confirmed using DNA fragmentation, terminal deoxyribonucelotidyl transferase-mediated dUTP nick end labeling and by 4,6-diamidino-2-phenylindole staining. Microscopy was used to observe apoptotic cell morphology. Western blotting was used to investigate the protein expression of known apoptotic mediators including cytochrome c, caspase-3, and PARP. The apoptosis triggered by myristicin was accompanied by an accumulation of cytochrome c and by the activation of caspase-3. The results obtained suggest that myristicin induces cytotoxicity in human neuroblastoma SK-N-SH cells by an apoptotic mechanism. This myristicin-induced apoptosis provides further insight of the molecular mechanisms of myristicin toxicity.
Lee
Bo Kyung
BK
Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoeki-dong, Dongdeamoon-ku, Seoul 130-701, Republic of Korea.
Kim
Jae Hee
JH
Jung
Ji Wook
JW
Choi
Ji Woong
JW
Han
Eui Sik
ES
Lee
Sun Hee
SH
Ko
Kwang Ho
KH
Ryu
Jong Hoon
JH
D000081248:Allylbenzene Derivatives; D017209:Apoptosis / Q000187:drug effects*; D001593:Benzyl Compounds / Q000494:pharmacology* / Q000633:toxicity*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis / Q000494:pharmacology; D045304:Cytochromes c / Q000096:biosynthesis / Q000494:pharmacology; D004249:DNA Damage; D004148:Dioxolanes / Q000494:pharmacology* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D009447:Neuroblastoma / Q000473:pathology*; D011748:Pyrogallol / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000081248:Allylbenzene Derivatives; D001593:Benzyl Compounds; D004148:Dioxolanes; D011748:Pyrogallol; C005246:myristicin; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases