| Kinase Assay: |
| Planta Med. 2003 May;69(5):445-51. | | Simultaneous analysis of seventeen chemical ingredients of Ligusticum chuanxiong by on-line high performance liquid chromatography-diode array detector-mass spectrometry.[Pubmed: 24058374 ] | Glutathione S-transferase (GST) is the key enzyme in multidrug resistance (MDR) of tumour.
Inhibition of the expression or activity of GST has emerged as a promising therapeutic strategy for the reversal of MDR.
METHODS AND RESULTS:
Coniferyl ferulate (CF), isolated from the root of Angelica sinensis (Oliv.) Diels (Radix Angelicae sinensis, RAS), showed strong inhibition of human placental GST. Its 50% inhibition concentration (IC50) was 0.3 μ M, which was greater than a known GSTP1-1 inhibitor, ethacrynic acid (EA), using the established high-throughput screening model. Kinetic analysis and computational docking were used to examine the mechanism of GST inhibition by CF. Computational docking found that CF could be fully docked into the gorge of GSTP1-1. The further exploration of the mechanisms showed that CF was a reversible noncompetitive inhibitor with respect to GSH and CDNB, and it has much less cytotoxicity. Apoptosis and the expression of P-gp mRNA were evaluated in the MDR positive B-MD-C1 (ADR+/+) cell line to investigate the MDR reversal effect of CF. Moreover, CF showed strong apoptogenic activity and could markedly decrease the overexpressed P-gp.
CONCLUSIONS:
The results demonstrated that CF could inhibit GST activity in a concentration-dependent manner and showed a potential MDR reversal effect for antitumour adjuvant therapy. | | Evid Based Complement Alternat Med. 2013;2013:639083. | | Coniferyl Ferulate, a Strong Inhibitor of Glutathione S-Transferase Isolated from Radix Angelicae sinensis, Reverses Multidrug Resistance and Downregulates P-Glycoprotein.[Pubmed: 24058374 ] | Glutathione S-transferase (GST) is the key enzyme in multidrug resistance (MDR) of tumour. Inhibition of the expression or activity of GST has emerged as a promising therapeutic strategy for the reversal of MDR.
METHODS AND RESULTS:
Coniferyl ferulate (CF), isolated from the root of Angelica sinensis (Oliv.) Diels (Radix Angelicae sinensis, RAS), showed strong inhibition of human placental GST. Its 50% inhibition concentration (IC50) was 0.3 μ M, which was greater than a known GSTP1-1 inhibitor, ethacrynic acid (EA), using the established high-throughput screening model. Kinetic analysis and computational docking were used to examine the mechanism of GST inhibition by CF. Computational docking found that CF could be fully docked into the gorge of GSTP1-1. The further exploration of the mechanisms showed that CF was a reversible noncompetitive inhibitor with respect to GSH and CDNB, and it has much less cytotoxicity. Apoptosis and the expression of P-gp mRNA were evaluated in the MDR positive B-MD-C1 (ADR+/+) cell line to investigate the MDR reversal effect of CF. Moreover, CF showed strong apoptogenic activity and could markedly decrease the overexpressed P-gp.
CONCLUSIONS:
The results demonstrated that CF could inhibit GST activity in a concentration-dependent manner and showed a potential MDR reversal effect for antitumour adjuvant therapy. |
|
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