Honokiol inhibits HepG2 migration via down‐regulation of IQGAP1 expression discovered by a quantitative pharmaceutical proteomic analysis |
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| Authors: | Shufang Liang Afu Fu Qiang Zhang Minghai Tang Jin Zhou Yuquan Wei Lijuan Chen |
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| Institution: | 1. State Key Laboratory of Biotherapy and Cancer Centre, West China Hospital, West China Medical School, Sichuan University, Chengdu, P. R. China;2. These authors have contributed equally to this work. |
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| 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 μg/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. |
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| Keywords: | Cell biology Cell migration Honokiol Quantitative proteomics Ras GTPase‐activating‐like protein Stable isotope labeling by amino acids in cell culture |
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