GMI, a fungal immunomodulatory protein from Ganoderma microsporum, induce apoptosis via ß-catenin suppression in lung cancer cells.

ABSTRACT

ß-catenin is important in development of lung cancer. In our previous study, GMI, a fungal immunomodulatory protein, inhibits lung cancer cell survival. The aim of this study is to evaluate the effect of GMI on ß-catenin inhibition and apoptosis induction. GMI induced apoptosis in lung cancer cells bearing wild-type and mutated EGFR. GMI did not reduce the ß-catenin mRNA expression but suppressed the protein expressions of ß-catenin that resulted in the transcriptional downregulation of its target genes survivin and cyclin-D1. The transcriptional activation activity of ß-catenin was demonstrated by TOPFLASH/FOPFLASH luciferase reporter assay. Inhibition of GSK-3ß and proteasome blocked the inhibiting effect of GMI on ß-catenin and its target genes. ß-catenin silencing increased activation of apoptosis in GMI-treated H1355 cells. This is the first study to reveal the novel function of GMI in inducing apoptosis via ß-catenin inhibition. These results provide a new potential of GMI in against lung cancer.