Ganodermanontriol inhibits proliferation and invasiveness of human breast cancer cells by the down‐regulation of survivin and uPA signaling

Abstract

In the present study, we investigated the effects of Ganodermanontriol (GT), triterpene isolated from an oriental medical mushroom Ganoderma lucidum, on the growth and invasiveness of human breast cancer cells. Although we have previously demonstrated that G. lucidum extract suppresses proliferation, invasive behavior and angiogenesis of cancer cells, the effect of GT on breast cancer cells have not been addressed. Here, we show that GT suppressed proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231 in a time- and dose- dependent manner. GT also suppressed secretion of urokinase plasminogen activator (uPA), resulting in the inhibition of cell migration, cell adhesion to the extracellular matrix (ECM) protein vitronectin (VN), and suppression of invasion of breast cancer cells through matrigel. In addition, GT treatment markedly changed expression of 511 genes as assessed by DNA-microarray. In conclusion, our results demonstrate that GT inhibit the growth and the invasive behavior of breast cancer cells through the down-regulation of survivin expression and inhibition of the formation of uPA-uPAR-VN-integrin complex.