Honokiol inhibits HepG2 migration via down-regulation of IQGAP1 expression discovered by a quantitative pharmaceutical proteomic analysis.

Abstract	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.
Authors	Shufang Liang, Afu Fu, Qiang Zhang, Minghai Tang, Jin Zhou, Yuquan Wei, Lijuan Chen
Journal	Proteomics (Proteomics) Vol. 10 Issue 7 Pg. 1474-83 (Apr 2010) ISSN: 1615-9861 [Electronic] Germany
PMID	20127691 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents, Phytogenic Biphenyl Compounds IQ motif containing GTPase activating protein 1 Lignans Proteome ras GTPase-Activating Proteins honokiol cdc42 GTP-Binding Protein rac1 GTP-Binding Protein
Topics	Animals Antineoplastic Agents, Phytogenic (pharmacology) Biphenyl Compounds (pharmacology) Cell Movement (drug effects) Down-Regulation (drug effects) Hep G2 Cells Histocytochemistry Humans Isotope Labeling Lignans (pharmacology) Mice Mice, Nude Proteome (drug effects) Proteomics (methods) Reproducibility of Results Statistics, Nonparametric Tumor Burden cdc42 GTP-Binding Protein (metabolism) rac1 GTP-Binding Protein (metabolism) ras GTPase-Activating Proteins (biosynthesis, genetics)

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