Inhibition of GLS suppresses proliferation and promotes apoptosis in prostate cancer.

Altered glutamine metabolism is a hallmark of cancer growth, forming the theoretical basis for development of metabolic therapies as cancer treatments. Glutaminase (GLS), a crucial enzyme involved in the regulation of glutamine metabolism, has been reported to play crucial roles in cancer development. However, the precise function of GLS in prostate cancer (PCa) remains unclear. The purpose of the present study was to assess the GLS expression and its clinical significance in PCa. We found that GLS was significantly up-regulated in PCa tissues and cell lines. High expression of GLS was significantly associated with Gleason score (P=0.001) and Tumor stage (P=0.015). Functionally, we silenced GLS in PCa cell lines and revealed that GLS knockdown largely blunted the proliferation of DU145 and PC-3 cells. Mechanistically, we demonstrated that knockdown of GLS induced apoptosis and cell cycle arrest. Moreover, we observed that the expressions of Bax were increased while the levels of cyclinD1 and Bcl-2 were decreased after knockdown of GLS in PCa cells. Importantly, through Western blot analysis, we identified that GLS knockdown dramatically suppressed Wnt/beta-catenin pathway. Taken together, GLS is a novel oncogene in PCa and may be a potential treatment target for PCa patients.