Prostate cancer is one of the most frequently diagnosed malignancies among men worldwide. Increasing evidence suggests that metabolic reprogramming, particularly glutamine metabolism, plays a critical role in tumor growth and survival. Glutaminase (GLS), a key enzyme responsible for converting glutamine to glutamate, has emerged as a potential therapeutic target in several cancer types. CB-839 is a selective glutaminase inhibitor that has shown promising antitumor activity in preclinical studies. Based on the importance of glutamine metabolism in cancer progression, we hypothesized that inhibition of glutaminase by CB-839 may suppress prostate cancer cell proliferation and migration.

In this study, the anticancer effects of CB-839 were investigated in the human prostate cancer cell line PC-3, while the non-tumorigenic prostate epithelial cell line PNT1-A was used as a control. Cells were treated with CB-839 and analyzed at 24, 48, and 72 hours. Cell viability was assessed using the MTT assay. The effect of CB-839 on cell migration was evaluated by migration assays, and long-term proliferative capacity was examined using colony formation assays. In addition, caspase-3 activity was measured using a colorimetric caspase activity assay to evaluate apoptosis following CB-839 treatment.

The results demonstrated that CB-839 treatment significantly reduced the viability of PC-3 prostate cancer cells in a time-dependent manner, whereas its effect on PNT1-A cells was comparatively limited. Migration assays revealed a marked decrease in the migratory capacity of PC-3 cells following CB-839 exposure. Furthermore, colony formation assays indicated a substantial reduction in clonogenic survival in treated cancer cells. Increased caspase activity suggested that CB-839 may induce apoptosis in PC-3 cells.

Taken together, our findings indicate that glutaminase inhibition by CB-839 suppresses proliferation, migration, and clonogenic potential of prostate cancer cells while promoting apoptotic cell death. These results support the potential of targeting glutamine metabolism as a therapeutic strategy in prostate cancer and highlight CB-839 as a promising candidate for further investigation.

This work was supported by the Scientific Research Projects Coordination Unit of Yıldız Technical University (BAP). The authors declare no conflict of interest.