Gallein, a Gβγ subunit signalling inhibitor, inhibits metastatic spread of tumour cells expressing OR51E2 and exposed to its odorant ligand

Abstract

Objective: We previously reported that the olfactory receptor OR51E2, overexpressed in LNCaP prostate cancer cells, promotes cell invasiveness upon stimulation of its agonist β-ionone, and this phenomenon increases metastatic spread. Furthermore, we showed that the induced cell invasiveness involves a PI3 kinase dependent signalling pathway. We report here the results of a new investigation to address whether gallein, a small inhibitor of G protein βγ subunit interaction with PI3 kinase, can inhibit β-ionone effects both in vitro and in vivo. Results: We demonstrate that gallein can inhibit the β-ionone-induced cell invasiveness in vitro, as well as the spread of metastases in vivo. LNCaP cell invasiveness, assessed using spheroid cultures in collagen gels in vitro, was increased by β-ionone and the effect was reversed by co-administration of gallein. LNCaP tumour cells, subcutaneously inoculated to immunodeficient mice, generated more metastases in vivo when β-ionone was applied through the skin. Furthermore, the intraperitoneal injection of gallein inhibited this increased metastasis spread. Our results thus support the role of OR51E2 in the β-ionone observed effects, and suggest that gallein could be a potential new agent in personalized medicine of the tumours expressing OR51E2.