1. 18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes.
- Author
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Shetty AV, Thirugnanam S, Dakshinamoorthy G, Samykutty A, Zheng G, Chen A, Bosland MC, Kajdacsy-Balla A, and Gnanasekar M
- Subjects
- Animals, Antineoplastic Agents pharmacology, Cattle, Cell Growth Processes drug effects, Cell Line, Tumor, Down-Regulation drug effects, Endothelial Cells drug effects, Glycyrrhetinic Acid pharmacology, Humans, Male, Matrix Metalloproteinase 9 biosynthesis, Matrix Metalloproteinase 9 genetics, Neovascularization, Pathologic drug therapy, Neovascularization, Pathologic pathology, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Transcription Factor RelA biosynthesis, Transcription Factor RelA genetics, Vascular Endothelial Growth Factor A biosynthesis, Vascular Endothelial Growth Factor A genetics, Gene Expression Regulation, Neoplastic drug effects, Glycyrrhetinic Acid analogs & derivatives, Inflammation genetics, Prostatic Neoplasms drug therapy, Prostatic Neoplasms genetics
- Abstract
Glycyrrhetinic acid is an active triterpenoid metabolite of glycyrrhizin abundantly present in licorice roots. Glycyrrhetinic acid exists as α and β stereo-isomeric forms. Both stereo-isomeric forms are known to have anti-inflammatory and anticancer activity. However, the effects and anticancer mechanism of α glycyrrhetinic acid in prostate cancer cells has not yet been evaluated. Therefore, we investigated the growth inhibition, induction of apoptosis and the anticancer mechanisms of 18α-glycyrrhetinic acid (AGA), on the androgen-independent metastatic prostate cancer cell line DU-145. Our results showed that AGA inhibited proliferation and growth of these cells by inducing apoptosis as determined by Annexin V and flow cytometry analyses. Our studies also showed that HUVEC tube formation was drastically reduced when cultured in conditioned medium of AGA-treated DU-145 cells. In addition, AGA treatment prevented the invasion of DU-145 prostate cancer cells on matrigel coated transwells via down-regulation of NF-κB (p65), VEGF and MMP-9 expression. Furthermore, AGA treatment also down-regulated the expression of pro-inflammatory cytokine/growth factor genes HMGB1, IL-6 and IL-8 in DU-145 cells. Interestingly, AGA simultaneously upregulated the expression of non-steroidal anti-inflammatory gene-1 (NAG-1) in DU-145 cells suggesting its anti-inflammatory activity on prostate cancer cells. Taken together, the results of this study suggest that AGA may be a promising anticancer agent that merits further investigation for the chemoprevention and treatment of prostate cancer.
- Published
- 2011
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