Investigation of the anticancer activity of DCZ0415, a small molecular inhibitor of TRIP13, in U87 human glioblastoma multiforme cells

Aim: Thyroid Hormone Receptor Interacting Protein 13 (TRIP13) is a protein involved in spindle-aggregation checkpoint, which plays a role in meiotic recombination. Recent studies have revealed that TRIP13 may be a potential tumor inducer in many cancers, including glioblastoma multiforme (GBM). We aimed to investigate the anticancer activity of DCZ0415, a small molecule inhibitor of TRIP13, in U87 human GBM cells in this study.

Materials and Methods: The possible anticancer effect of DCZ0415 on U87 cells was determined by cytotoxicity, colony formation, and apoptosis assays. In addition, the effects of DCZ0415 on mRNA levels of genes which were involved in apoptosis, invasion and Transforming Growth Factor-Beta (TGF-β) signaling pathway were investigated by qRT-PCR analysis.

Results: DCZ0415 inhibited U87 cell proliferation in a dose and time dependent manner. The IC₅₀ dose of DCZ0415 for 48 hours was determined as 19.77 µM in U87 cells. DCZ0415 treatment at this dose induced apoptosis and suppressed colony forming abilities of U87 cells. In addition, DCZ0415 altered mRNA levels of genes associated with apoptosis, invasion and TGF-β signaling pathway, which could lead to anticancer effects.

Conclusion: DCZ0415, an inhibitor of TRIP13 which has been evaluated as a new oncogenic factor in cancer, has an anticancer effect on GBM cells. In this respect, it is thought that TRIP13 may be an important therapeutic target for GBM and DCZ0415 may be considered as an effective inhibitor that causes anticancer effects in GBM cells.