title: Involvement of BID translocation in glycyrrhetinic acid and 11-deoxy glycyrrhetinic acid-induced attenuation of gastric cancer growth.
abstract: Glycyrrhetinic acid (GA), the main chemical constituents of licorice, has shown remarkable anticancer activity. However, the side effects limit its widespread use. 11-DOGA is produced through reduction of GA 11-carbonyl to 11-hydroxyl to reduce its side effects, although its anticancer activities are largely unknown. Here, we report that the functional mechanisms of GA and 11-DOGA in gastric cancers, as well as the comparison between these two drugs' pharmacological potential. Firstly, we found that GA and 11-DOGA significantly inhibits the viabilities of gastric cancer cells in dose- and time-dependent manners. Both GA and 11-DOGA induce gastric cancer cells apoptosis and cell cycle arrest in G2 phase by upregulation of p21 and downregulation of cdc2 and cyclin B1. Further studies show that GA and 11-DOGA-induced apoptosis in gastric cancer cells is associated with BID translocation from nucleus to mitochondria. Moreover, GA and 11-DOGA could effectively inhibit tumor formation of gastric cancer cells in nude mice. Comparing with 11-DOGA, GA presents higher toxicity toward gastric cancer cells both in vivo and in vitro. Thus, the elucidation of the functional mechanisms of GA and 11-DOGA-induced attenuation of gastric cancer growth suggests a possible therapeutic role of GA and its derivatives.
authors.affiliation: a Cancer Research Center, Medical College of Xiamen University , Xiamen , People's Republic of China.
authors.forename: Dejian
authors.initials: D
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Zhong
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Song
authors.forename: Tianhui
authors.initials: T
authors.lastname: Hu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016195:G2 Phase / Q000187:drug effects; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008819:Mice, Nude; D021381:Protein Transport / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: C000597837:11-deoxy glycyrrhetinic acid; D000972:Antineoplastic Agents, Phytogenic; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D045304:Cytochromes c; D006034:Glycyrrhetinic Acid