Honokiol inhibits HepG2 migration via down-regulation of IQGAP1 expression discovered by a quantitative pharmaceutical proteomic analysis.
Honokiol (HNK), a natural small molecular product, inhibited proliferation of HepG2 cells and exhibited anti-tumor activity in nude mice. In this article, we applied a novel sensitive stable isotope labeling with amino acids in cell culture-based quantitative proteomic method and a model of nude mice to investigate the correlation between HNK and the hotspot migration molecule Ras GTPase-activating-like protein (IQGAP1). The quantitative proteomic analysis showed that IQGAP1 was 0.53-fold down-regulated under 10 microg/mL HNK exposure for 24 h on HepG2 cells. Migration ability of HepG2 cells under HNK treatment was correlated with its expression level of IQGAP1. In addition, the biochemical validation on HepG2 cells and the tumor xenograft model further demonstrated that HNK decreased the expression level of IQGAP1 and its upstream proteins Cdc42/Rac1. These data supported that HNK can modulate cell adhesion and cell migration by acting on Cdc42/Rac1 signaling via IQGAP1 interactions with its upstream Cdc42/Rac1 proteins, which is a new molecular mechanism of HNK to exert its anti-tumor activity.
Liang
Shufang
S
State Key Laboratory of Biotherapy and Cancer Centre, West China Hospital, West China Medical School, Sichuan University, Chengdu, PR China.
Fu
Afu
A
Zhang
Qiang
Q
Tang
Minghai
M
Zhou
Jin
J
Wei
Yuquan
Y
Chen
Lijuan
L
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006651:Histocytochemistry; D006801:Humans; D007553:Isotope Labeling; D017705:Lignans / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D020543:Proteome / Q000187:drug effects; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D018709:Statistics, Nonparametric; D047368:Tumor Burden; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000096:biosynthesis* / Q000235:genetics; D000498:Allyl Compounds; D010636:Phenols
D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D017705:Lignans; D020543:Proteome; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020703:ras GTPase-Activating Proteins; C101203:IQ motif containing GTPase activating protein 1; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols