Background/Aim: Triple-negative breast cancer (TNBC) is most the aggressive type of breast cancer and is poorly responsive to endocrine therapeutics; however, one of the most attractive treatments is tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based therapies. To identify compounds that enhance the efficacy of TRAIL-based therapies, we screened 55 compounds from natural products in combination with TRAIL in TNBC cells.

Human TNBC cells, MDA-MB-468 and MDA-MB-231, and murine TNBC cells, 4T1, were used. Cell viability, apoptotic cells, and cell cycle were quantified by the WST-1 assay, annexin-V/7-amino-actinomycinD (7-AAD) staining and Propidium iodide (PI) staining, respectively. In vivo effects of piperine were evaluated in the orthotopic-inoculated 4T1-luc mouse model.

After screening, we identified piperine as the most potent adjuvant at enhancing the efficacy of TRAIL-based therapies in TNBC cells in vitro and in vivo, which might be mediated through inhibition of survivin and p65 phosphorylation.

Piperine may enhance TRAIL-based therapeutics for TNBC.