Interruption of Lung Cancer Cell Migration and Proliferation by Fungal Immunomodulatory Protein FIP-fve from Flammulina velutipes

Abstract

FIP-fve is an immunomodulatory protein isolated from Flammulina velutipes that possesses anti-inflammatory and immunomodulatory activities. However, little is known about its anticancer effects. It is suppressed cell proliferation of A549 lung cancer cells on MTT assay following 48 h treatment of FIP-fve. FIP-fve treatment also resulted in cell cycle arrest but not apoptosis on flow cytometry. This immunomodulatory protein was observed to increase p53 expression, as well as the expression of its downstream gene p21, on Western blot. FIP-fve inhibited migration of A549 cells on wound healing assay and decreased filopodia fiber formation on labeling with Texas Red-X phalloidin. To confirm the effect of FIP-fve on the role of Rac1 in filopodia formation, we investigated the activity of Rac1 in A549 cells following FIP-fve treatment. FIP-fve inhibited EGF-induced activation of Rac1. We demonstrated that FIP-fve decreases RACGAP1 mRNA and protein levels on RT-PCR and Western blot. In addition, the reporter activity of RACGAP1 was reduced by FIP-fve on RacGAP1 promoter assay. Silencing of RacGAP1 decreased cell migration, and overexpression of RacGAP1 increased cell migration in A549 cells. In conclusion, FIP-fve inhibits lung cancer cell migration via RacGAP1 and suppresses the proliferation of A549 via p53 activation pathway.

Recombinant Expression of a Novel Fungal Immunomodulatory Protein with Human Tumor Cell Antiproliferative Activity from Nectria haematococca

“…These observations suggest that FIPs can be therapeutic. Suppression of tumor cell growth is associated with an increase in polyfunctional T cells that secrete multiple effector cytokines, such as IL-2, IFN-γ and IL-17 [39,40]. The potential mechanism for rFIP-nha induced apoptotic effects needs to be further explored.…”

Golden Needle Mushroom: A Culinary Medicine with Evidenced-Based Biological Activities and Health Promoting Properties

“…Fungal immunomodulatory protein, FIP-fve, mainly extracted from fruiting body of F. velutipes has been studied extensively and explored for its diverse bioactivities including immunomodulatory, anticancer and anti-inflammatory properties (Chang et al, 2013, 2014; Lee et al, 2013). Ribosome inactivating proteins such as flammin, velin, velutin and flammulin are present in the fruiting bodies and extract of the mushroom (Wang and Ng, 2000, 2001; Ng and Wang, 2004).…”

Identification and functional characterization of a novel fungal immunomodulatory protein from Postia placenta

“…FIPs can agglutinate erythrocytes (Kino et al, 1989;Ko et al, 1995), stimulate lymphocyte mitogenesis (Haak-Frendscho et al, 1993;Murasugi et al, 1991;Van der Hem et al, 1996), promote the release of TH1-specific cytokines (interleukin-2, IL-2; interferon-γ, IFN-γ; and tumor necrosis factor β, TNF-β) , interrupt tumor cell proliferation (Chang et al, 2013) and induce tumor cell apoptosis (Liao et al, 2006(Liao et al, , 2007Lin et al, 2009). In vivo, FIPs also inhibit systemic anaphylaxis via reduction of antibody production during the Arthus reactions (Hsieh et al, 2003;Kino et al, 1991;Ko et al, 1995).…”