UNBS5162 induces growth inhibition and apoptosis via inhibiting PI3K/AKT/mTOR pathway in triple negative breast cancer MDA-MB-231 cells

Abstract

UNBS5162, a naphthalimide derivative, has a strong anticancer effect and low clinical hematological toxicity. UNBS5162 has been shown to have an anticancer effect in numerous cancer types, except triple negative breast cancer (TNBC). To explore this issue, TNBC MDA-MB-231 cells were selected, and the effect of UNBS5162 on their growth, proliferation and motility regulation was investigated in vitro. The results showed that UNBS5162 significantly inhibited the proliferation, migration and invasion of TNBC cells. In addition, the level of pro-apoptosis protein Bcl-2-associated X protein and active caspase-3 increased, but apotptosis regulator BCL-2 decreased in MDA-MB-231 cells after UNBS5162 treatment, which demonstrated UNBS5162 treatment triggered cell apoptosis. Moreover, UNBS5162 reduced the phosphorylation levels of AKT serine/threonine kinase (AKT), mechanistic target of rapamycin kinase (mTOR), P70S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 in the phosphatidylinositol 3-kinase/AKT/mTOR (PAM) signaling pathway, which plays a critical role in cell proliferation, and apoptosis. Altogether, the results of the present study suggest that UNBS5162 effectively induces the growth inhibition and apoptosis of TNBC cells through regulation of the PAM pathway, which may be a candidate target for TNBC treatment.