title: Synthesis and in vitro and in vivo antitumour activity study of 11-hydroxyl esterified bergenin/cinnamic acid hybrids.
abstract: Fourteen bergenin/cinnamic acid hybrids were synthesized, characterized and evaluated for their antitumour activity both in vitro and in vivo. The most potent compound, 5c, arrested HepG2 cells (IC50= 4.23 ± 0.79 μM) in the G2/M phase and induced cellular apoptosis. Moreover, compound 5c was also found to suppress the tumour growth in Heps xenograft-bearing mice with low toxicity. In the mechanistic study, 5c administration ignited a mitochondria-mediated apoptosis pathway of HepG2 cell death. Furthermore, 5c activated Akt-dependent pathways and further decreased the expression of the Bcl-2 family of proteins. The downstream mitochondrial p53 translocation was also significantly activated, accompanied by an increase of the caspase-9, caspase-3 activation. These data imply that bergenin/cinnamic acid hybrids could serve as novel Akt/Bcl-2 inhibitors for further preclinical studies.
authors.affiliation: Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China; Xi'an Taikomed Pharmaceutical Technology Co., LTD, Xi'an 710077, People's Republic of China. Electronic address: chengyuanliang@gmail.com.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Liang
authors.affiliation: Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China.
authors.forename: Shaomeng
authors.initials: S
authors.lastname: Pei
authors.affiliation: Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Ju
authors.affiliation: Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China.
authors.forename: Minyi
authors.initials: M
authors.lastname: Jia
authors.affiliation: Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China.
authors.forename: Danni
authors.initials: D
authors.lastname: Tian
authors.affiliation: Xi'an Taikomed Pharmaceutical Technology Co., LTD, Xi'an 710077, People's Republic of China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China. Electronic address: maogn@sust.edu.cn.
authors.forename: Gennian
authors.initials: G
authors.lastname: Mao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002934:Cinnamates / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D004951:Esterification; D005260:Female; D016195:G2 Phase; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D002934:Cinnamates; D019253:Proto-Oncogene Proteins c-bcl-2; C029010:cinnamic acid; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9; C006741:bergenin
keywords: Akt/Bcl-2; Antitumour; Apoptosis; Bergenin; Cinnamic acid