chebulagic-acid and Liver-Neoplasms

chebulagic-acid has been researched along with Liver-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for chebulagic-acid and Liver-Neoplasms

ArticleYear
Chebulagic acid synergizes the cytotoxicity of doxorubicin in human hepatocellular carcinoma through COX-2 dependant modulation of MDR-1.
    Medicinal chemistry (Shariqah (United Arab Emirates)), 2011, Volume: 7, Issue:5

    Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) specific inhibitors are anti-inflammatory agents that have also shown to be useful in anticancer therapy. The effects of chebulagic acid (CA), a benzopyran tannin from Terminalia chebula having COX-2/5-LOX dual inhibitory properties, on the sensitivity of doxorubicin (Dox) in human hepatocellular carcinoma cell line HepG2 were studied in the present investigation. CA increased the accumulation of Dox in a concentration dependant manner and also enhanced the cytotoxicity of Dox in HepG2 cells by 20 folds. Quantitation of interaction by calculating Combination Index (CI) showed a strong synergistic interaction between CA and Dox in terms of cell growth inhibition. Calculation of dose reduction index (DRI) for CA-Dox combinations also showed a significant decrease in the dosage of Dox in the presence of CA. The induction of MDR1 expression by PGE(2), a metabolite of COX-2, and its downregulation by COX-2 knockdown or CA implies that the enhanced sensitivity of HepG2 cells to doxorubicin by CA is mediated by the downregulation of MDR1 expression, via COX-2-dependent mechanism. Further studies reveal the inactivation of signal transduction pathways involving Akt, ERK, JNK and p38 and the transcription factor NF-κB in the CA induced down regulation of MDR1. The present study shows the efficacy of CA to overcome MDR-1 mediated drug resistance in HepG2 cells through COX-2 dependant modulation of MDR-1.

    Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzopyrans; Carcinoma, Hepatocellular; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Doxorubicin; Drug Screening Assays, Antitumor; Glucosides; Humans; Liver Neoplasms; Structure-Activity Relationship; Tumor Cells, Cultured

2011