Poncirus trifoliata Rafin. induces the apoptosis of triple‑negative breast cancer cells via activation of the c‑Jun NH(2)‑terminal kinase and extracellular signal‑regulated kinase pathways

Background: Poncirus trifoliata Rafin. is a traditional medicine with known anti‑inflammatory and anti‑cancer properties. Traditionally, it is used to control chronic inflammation, allergy and gastrointestinal diseases such as digestive ulcers gastritis in China, Japan, and Korea. Objectives: To evaluate the apoptosis‑inducing activity of a P. trifoliata methanol extract (MEPT) and elucidate the molecular mechanisms. Materials and Methods: The anti‑cancer effect of MEPT and its underlying mechanisms were investigated in breast cancer cells using 3,4,5‑dimethyl N‑methylthiazol‑2‑yl‑2, 5‑d‑phenyl tetrazolium bromide assay, cell cycle analysis, and western blotting. Results: MEPT suppressed the proliferation of MDA‑MB‑231 cells with inhibition dose 50% value of 119.44 μg/mL at 24 h, which have features typical of triple‑negative breast cancer cells. MEPT also altered the characteristic features of the MDA‑MB‑231 cells and increased the proportion of cells undergoing sub‑G1 arrest. In addition, MEPT increased levels of caspase 8 and 3 in MDA‑MB‑231 cells, whereas caspase 9 was not detected. In addition, MEPT‑induced tumor necrosis factor receptor (TNFR) and TNFR type 1‑associated death domain (TRADD) protein and the activations of c‑Jun NH(2)‑terminal kinase (JNK) and extracellular signal‑regulated kinases (ERK). Conclusion: Our results indicate that MEPT has chemotherapeutic potential in triple‑negative breast cancer and that at the molecular level its effects are derived from the activations of TNFR and of the mitogen‑activated protein kinase pathway.