title: 18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes.
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.
authors.affiliation: Department of Biomedical Sciences, University of Illinois, College of Medicine, Rockford, IL 61107, USA.
authors.forename: Aditya V
authors.initials: AV
authors.lastname: Shetty
authors.forename: Sivasakthivel
authors.initials: S
authors.lastname: Thirugnanam
authors.forename: Gajalakshmi
authors.initials: G
authors.lastname: Dakshinamoorthy
authors.forename: Abhilash
authors.initials: A
authors.lastname: Samykutty
authors.forename: Guoxing
authors.initials: G
authors.lastname: Zheng
authors.forename: Aoshuang
authors.initials: A
authors.lastname: Chen
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Bosland
authors.forename: André
authors.initials: A
authors.lastname: Kajdacsy-Balla
authors.forename: Munirathinam
authors.initials: M
authors.lastname: Gnanasekar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002417:Cattle; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D051996:Transcription Factor RelA; D042461:Vascular Endothelial Growth Factor A; C119129:18alpha-glycyrrhetinic acid; D020780:Matrix Metalloproteinase 9; D006034:Glycyrrhetinic Acid