Effects of (1R,9S)-beta-hydrastine on l-DOPA-induced cytotoxicity in PC12 cells.
(1R,9S)-beta-Hydrastine in lower concentrations of 10-50 microM inhibits dopamine biosynthesis in PC12 cells. In this study, the effects of (1R,9S)-beta-hydrastine on L-DOPA (L-3,4-dihydroxyphenylalanine)-induced cytotoxicity in PC12 cells were investigated. (1R,9S)-Hydrastine at concentrations up to 250 microM did not reduce cell viability. However, at concentrations higher than 500 microM it caused cytotoxicity in PC12 cells, as determined with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, TUNEL (terminal deoxynucleotidyltransferase dUTP nick-end labeling) method and flow cytometry. Exposure of PC12 cells to cytotoxic concentrations of (1R,9S)-beta-hydrastine (500 and 750 microM) in combination with L-DOPA (20, 50 and 100 microM) after 24 or 48 h resulted in a significant decrease in cell viability compared with the effects of (1R,9S)-beta-hydrastine or L-DOPA alone, and apoptotic cell death was observed. However, the decrease in cell viability induced by (1R,9S)-beta-hydrastine was not prevented by the antioxidant N-acetyl-L-cysteine, indicating that it is not mediated by membrane-based oxygen free radical damage. These data suggest that (1R,9S)-beta-hydrastine has a mild cytotoxic effect and at higher concentration ranges aggravates L-DOPA-induced cytotoxicity in PC12 cells.
Yin
Shou Yu
SY
College of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University, San 48, Kaeshin-Dong, Heungduk-Gu, Cheongju 361-763, South Korea.
Lee
Jae Joon
JJ
Kim
Yu Mi
YM
Jin
Chun Mei
CM
Yang
Yoo Jung
YJ
Kang
Min Hee
MH
Kai
Masaaki
M
Lee
Myung Koo
MK
D000111:Acetylcysteine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D044182:Benzylisoquinolines; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D007536:Isomerism; D007980:Levodopa / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
D000470:Alkaloids; D000975:Antioxidants; D044182:Benzylisoquinolines; D015259:Dopamine Agents; D016166:Free Radical Scavengers; D007980:Levodopa; C013024:hydrastine; D000111:Acetylcysteine