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

Bin Lou; Jian Fan; Keyi Wang; Wei Chen; Xiaoqiong Zhou; Jie Zhang; Sha Lin; Feifei Lv; Yu Chen

doi:10.1016/j.yexcr.2013.08.010

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

Exp Cell Res. 2013 Oct 15;319(17):2708-17. doi: 10.1016/j.yexcr.2013.08.010. Epub 2013 Aug 16.

Authors

Bin Lou¹, Jian Fan, Keyi Wang, Wei Chen, Xiaoqiong Zhou, Jie Zhang, Sha Lin, Feifei Lv, Yu Chen

Affiliation

¹ Department of Laboratory Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.

PMID: 23958463
DOI: 10.1016/j.yexcr.2013.08.010

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.

Keywords: Cytotoxicity; Doxorubicin; Epithelial–mesenchymal transition; Hepatocellular carcinoma; N1-guanyl-1,7-diaminoheptane (GC7).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Carcinoma, Hepatocellular / drug therapy*
Doxorubicin / pharmacology*
Doxorubicin / therapeutic use
Epithelial-Mesenchymal Transition / drug effects*
Eukaryotic Translation Initiation Factor 5A
Guanine / analogs & derivatives*
Guanine / pharmacology
Guanine / therapeutic use
Hep G2 Cells
Humans
Liver Neoplasms / drug therapy*
Peptide Initiation Factors / antagonists & inhibitors*
Peptide Initiation Factors / genetics
Peptide Initiation Factors / metabolism
RNA-Binding Proteins / antagonists & inhibitors*
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism

Substances

N(1)-guanyl-1,7-diaminoheptane
Peptide Initiation Factors
RNA-Binding Proteins
Guanine
Doxorubicin