title: N1-guanyl-1,7-diaminoheptane (GC7) enhances the therapeutic efficacy of doxorubicin by inhibiting activation of eukaryotic translation initiation factor 5A2 (eIF5A2) and preventing the epithelial-mesenchymal transition in hepatocellular carcinoma cells.
abstract: Hepatocellular carcinoma (HCC) cells undergo the epithelial-mesenchymal transition (EMT) during chemotherapy, which reduces the efficacy of doxorubicin-based chemotherapy. We investigated N1-guanyl-1,7-diaminoheptane (GC7) which inhibits eukaryotic translation initiation factor 5A2 (eIF5A2) activation; eIF5A2 is associated with chemoresistance. GC7 enhanced doxorubicin cytotoxicity in epithelial HCC cells (Huh7, Hep3B and HepG2) but had little effect in mesenchymal HCC cells (SNU387, SNU449). GC7 suppressed the doxorubicin-induced EMT in epithelial HCC cells; knockdown of eIF5A2 inhibited the doxorubicin-induced EMT and enhanced doxorubicin cytotoxicity. GC7 combination therapy may enhance the therapeutic efficacy of doxorubicin in HCC by inhibiting eIF5A2 activation and preventing the EMT.
authors: Department of Laboratory Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors: Bin
authors: B
authors: Lou
authors: Jian
authors: J
authors: Fan
authors: Keyi
authors: K
authors: Wang
authors: Wei
authors: W
authors: Chen
authors: Xiaoqiong
authors: X
authors: Zhou
authors: Jie
authors: J
authors: Zhang
authors: Sha
authors: S
authors: Lin
authors: Feifei
authors: F
authors: Lv
authors: Yu
authors: Y
authors: Chen
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D010448:Peptide Initiation Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D004317:Doxorubicin; D006147:Guanine; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C100667:N(1)-guanyl-1,7-diaminoheptane
keywords: Cytotoxicity; Doxorubicin; Epithelial–mesenchymal transition; Hepatocellular carcinoma; N1-guanyl-1,7-diaminoheptane (GC7)