Search

Summary: Triple-negative breast cancer (TNBC) contributes greatly to mortality of breast cancer, demanding new targetable options. We have shown that TNBC patients have high ΔNp63 expression in tumors. However, the function of ΔNp63 in established TNBC is yet to be explored. In current studies, targeting ΔNp63 with inducible CRISPR knockout and Histone deacetylase inhibitor Quisinostat showed that ΔNp63 is important for tumor progression and metastasis in established tumors by promoting myeloid-derived suppressor cell (MDSC) survival through tumor necrosis factor alpha. Decreasing ΔNp63 levels are associated with decreased CD4+ and FOXP3+ T-cells but increased CD8+ T-cells. RNA sequencing analysis indicates that loss of ΔNp63 alters multiple MDSC properties such as lipid metabolism, chemotaxis, migration, and neutrophil degranulation besides survival. We further demonstrated that targeting ΔNp63 sensitizes chemotherapy. Overall, we showed that ΔNp63 reprograms the MDSC-mediated immunosuppressive functions in TNBC, highlighting the benefit of targeting ΔNp63 in chemotherapy-resistant TNBC.

Olive (Olea europaea L.) leaf extract (OLE) have shown therapeutic activity against different types of cancer. However, it is less known that olive leaf extract has anti myeloma activity. The in vitro cytotoxic activity of OLE was evaluated against mouse metastatic melanoma B16F10 cell lines. The extracts were analyzed for their antioxidant activity by DPPH radical scavenging activity and the presence of bioactive compounds by liquid chromatography-electrospray ionization-tandem mass spectrometry respectively. The aqueous OLE induced apoptosis of B16F10 cells through ERK 1/2 and p53 mediated pathway. The metabolic profiling of OLE showed 23 metabolites notably oleuropein aglycone, apigenin, luteolin, tyrosol, oleuropein and hydroxytyrosol. Oleuropein present in OLE may be responsible for disrupting the activation of ERK1/2 receptor in melanoma B16F10 cell lines. These findings pave path for further investigations of the structure and function at the molecular level to establish the anticancer activity of oleuropein in melanoma skin cancer.