title: Synthesis and discovery of 18α-GAMG as anticancer agent in vitro and in vivo via down expression of protein p65.
abstract: Glycyrrhizic acid (GA) is a natural product with favorable antitumor activity. But, glycyrrhetinic acid monoglucuronide (GAMG) showed stronger antitumor activity than GA. It is of our interest to generate and identify novel compounds with regulation telomerase for cancer therapy. So, in this study, 18α-GAMG was synthesized via biotransformation. In vitro studies showed that it displayed potent anticancer activity and high selectivity on tumor liver cell SMMC-7721 versus human normal liver cell L-02. The further results in vivo confirmed that it could significantly improve pathological changes of N,N-diethylnitrosamine (DEN)-induced rat hepatic tumor. Western blot and immunofluorescence results indicated that the expression of p65-telomerase reverse transcriptase (TERT) was clearly down-regulated treated with it. Taken together, this study for the first time identified an active compound with high selectivity on tumor liver cell in mice. Furthermore, the title compound could inhibit the expression of protein p65 and TERT. These data support further studies to assess the rational design of more efficient p65 modulators in the future.
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, P. R. China.
authors.forename: Wen-jian
authors.initials: WJ
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, P. R. China.
authors.forename: Yong-an
authors.initials: YA
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, P. R. China.
authors.forename: He
authors.initials: H
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, P. R. China.
authors.forename: Jing-bo
authors.initials: JB
authors.lastname: Shi
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, P. R. China.
authors.forename: Xin-hua
authors.initials: XH
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004052:Diethylnitrosamine; D055808:Drug Discovery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D020035:Holoenzymes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020035:Holoenzymes; C482685:glycyrrhetic acid mono-glucuronide; D004052:Diethylnitrosamine; C509186:TERT protein, human; D019098:Telomerase; D006034:Glycyrrhetinic Acid