Effects of (1R,9S)-beta-hydrastine on l-DOPA-induced cytotoxicity in PC12 cells.

Shou Yu Yin, Jae Joon Lee, Yu Mi Kim, Chun Mei Jin, Yoo Jung Yang, Min Hee Kang, Masaaki Kai, Myung Koo Lee

Index: Eur. J. Pharmacol. 488(1-3) , 71-7, (2004)

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Abstract

(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.