Boron Derivatives Inhibit the Proliferation of Breast Cancer Cells and Affect Tumor-Specific T Cell Activity In Vitro by Distinct Mechanisms.

Breast cancer is the most frequently diagnosed cancer among women worldwide. Despite the initial clinical response obtained with the widely used conventional chemotherapy, an improved prognosis for breast cancer patients has been missing in the clinic because of the high toxicity to normal cells, induction of drug resistance, and the potential immunosuppressive effects of these agents. Therefore, we aimed to investigate the potential anti-carcinogenic effect of some boron derivatives (sodium pentaborate pentahydrate (SPP) and sodium perborate tetrahydrate (SPT)), which showed a promising effect on some types of cancers in the literature, on breast cancer cell lines, as well as immuno-oncological side effects on tumor-specific T cell activity. These findings suggest that both SPP and SPT suppressed proliferation and induced apoptosis in MCF7 and MDA-MB-231 cancer cell lines through downregulation of the monopolar spindle-one-binder (MOB1) protein. On the other hand, these molecules increased the expression of PD-L1 protein through their effect on the phosphorylation level of Yes-associated protein (Phospho-YAP (Ser127). In addition, they reduced the concentrations of pro-inflammatory cytokines such as IFN-γ and cytolytic effector cytokines such as sFasL, perforin, granzyme A, Granzyme B, and granulysin and increased the expression of PD-1 surface protein in activated T cells. In conclusion, SPP, SPT, and their combination could have growth inhibitory (antiproliferative) effects and could be a potential treatment for breast cancer. However, their stimulatory effects on the PD-1/PD-L1 signaling pathway and their effects on cytokines could ultimately account for the observed repression of the charging of specifically activated effector T cells against breast cancer cells.