A new immunomodulatory protein from Ganoderma microsporum inhibits epidermal growth factor mediated migration and invasion in A549 lung cancer cells

Abstract

Dysregulation of human epidermal growth factor receptor pathways by over-expression or constitutive activation can promote lung tumor processing including angiogenesis and metastasis and is associated with poor prognosis in non-small cell lung cancers. Ganoderma also known as Lingzhi has been one of the most popular chemoprevention mushrooms in East Asia for centuries. Among many bioactive components identified from Ganoderma, an immunomodulatory protein is the major ingredient for the treatment of lung cancer. Recombinant fungal immunomodulatory protein, GMI, was cloned from Ganoderma microsporum and purified. However, knowledge on the pharmacological and molecular mechanisms in suppressing EGF-mediated tumor invasion and metastasis is poorly understood. The goal of study is investigate in suppressing tumor invasion and metastasis activity of GMI. GMI exhibited an inhibitory effect on EGF-induced migration and invasion. GMI treatment with EGF presented the most potent anti-migration and anti-invasion properties on Boyden chamber assay. GMI inhibited EGF-induced phosphorylation and activation of EGFR and AKT pathway kinases in a dose-dependent manner. Additionally, the EGF-induced activation of Cdc42 GTPase was inhibited by GMI, while GMI had little effect on the EGF-induced activation of Rac1 GTPase. GMI also inhibited the EGF-induced microfilament depolymerization. These findings are the first to reveal the novel functions of GMI in tumor anti-metastasis and the molecular basis for its anticancer action.