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  • P-ISSN 1010-0695
  • E-ISSN 2288-3339

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Screening of β-Catenin/TCF Transcription Factor Inhibitors in Medicinal Herb Extracts

대한한의학회지 / Journal of Korean Medicine, (P)1010-0695; (E)2288-3339
2011, v.32 no.3, pp.35-43
Yedang Choe (Dongduk Women’s University)
Byungjo Na (Weedam Korean Hospital)
박세연 (Dongduk Women’s University)
Yedang, C. , Byungjo, N. , & 박세연. (2011). . 대한한의학회지, 32(3), 35-43.
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Abstract

Objectives: This study was performed to screen target-specific inhibitors of β-catenin/TCF signaling whose functional activation plays an important role in early events in carcinogenesis. Methods: To investigate the activation or suppression of β-catenin/TCF transcription, we established a transiently transfected cell line with a constitutively active β-catenin mutant gene whose product is not degraded. This cell line was also co-transfected with luciferase reporter gene constructs containing either an optimized (TOPflash) or mutant (FOPflash) TCF-binding element. We investigated cytotoxic effects using a 3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay. To find effective inhibitors of β- catenin/TCF signaling from medicinal herbs, the crude extracts of 99 types of medicinal herbs were screened using a luciferase assay system in HEK-293 and SH-SY5y cells. Results: At a concentration of 50 μg/ml, extracts of Angelica koreanae radix, Cannabis sativa semen, Ephedrae intermedia Schrenk radix, and Vitis rotundifolia fruit showed the following inhibitory effects on β-catenin/TCF signaling: 40 ± 5.6%, 23 ± 6.1%, 8 ± 5.1%, and 22 ± 9.8% in β-catenin-activated HEK-293 cells and 9 ± 4.7%, 39 ± 8.1%, 39 ± 6.4%, and 42 ± 10.1% in β-catenin-activated SH-SY5y cells, respectively. Crude extracts of E. radix were isolated by silica gel column chromatography, and two non-polar fractions of these extracts showed inhibitory effects on β-catenin/TCF signaling. Conclusions: In this study, we established a transiently transfected cell line as a screening system and found that various medicinal herb extracts had inhibitory effects on β-catenin/TCF signaling.

keywords
β-catenin/TCF signaling, carcinogenesis, screening, medicinal herb extract


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