Tetrandrine selectively protects against amyloid-beta protein - but not against MPTP-induced cytotoxicity in SK-N-SH neuroblastoma cells.
The evidence for loss of Ca2+ homeostasis due to neuronal degeneration is considerable and rapidly increasing. In this study, we try to evaluate the protective effect of tetrandrine (TET), an alkaloid isolated from the Chinese medicinal herb Radix Stephania tetrandrae S., on amyloid-beta protein (Abeta) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced cell death in SK-N-SH neuroblastoma cells. Both compounds reduced cell viability in a concentration-dependent manner after 72 h in culture. Cell proliferation in the presence of 20 microM Abeta or 0.4 mM MPTP was reduced to 58.3 +/- 4.9 or 54.9 +/- 5.5 %, respectively. TET (0.1, 0.5 and 1 microM) alone had no significant effect on cell survival; however, it prevented Abeta-induced cell death in a concentration-dependent manner. In contrast, TET failed to counteract MPTP-induced cytotoxicity. Also, an L-type calcium channel blocker, nimodipine, solely reversed Abeta-induced cell death. On the other hand, ELISA determination of mono-/oligo-nucleosomes accumulation showed that the mode of cell death evoked by Abeta was necrosis while that evoked by MPTP was presumably apoptosis. These results suggest that TET may mitigate the harmful effects of Abeta on cell survival, probably by interfering via the necrotic signal related to Ca2+ overloading through the L-type calcium channel.
Chiou
Wen-Fei
WF
National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC. wfchiou@cma23.nricm.edu.tw
Lee
Wan-Shin
WS
Yeh
Pen-Ho
PH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016229:Amyloid beta-Peptides / Q000633:toxicity; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D031609:Stephania tetrandra
D000470:Alkaloids; D016229:Amyloid beta-Peptides; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D010936:Plant Extracts; C009438:tetrandrine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine