The cytotoxic effects of propolis on breast cancer cells involve PI3K/Akt and ERK1/2 pathways, mitochondrial membrane potential, and reactive oxygen species generation

Abstract

Propolis has been extensively used to improve health and prevent inflammatory diseases. Different types of Cuban propolis (red, brown and yellow) have been documented. The purpose of this research was to investigate the cytotoxic effects of Cuban red propolis (CP) on MDA MB-231 cell line, since breast cancer is considered one of the most common causes of mortality among women. Antiproliferative and cytotoxic activity of CP against MDA MB-231 cells were determined by the 3-[4,5-dimethylth-iazol-2-yl]-2,5-diphenyl tetrazoliumbromide (MTT) and lactate dehydrogenase (LDH) assays. Apoptosis/necrosis, involvement of PI3K/Akt and ERK1/2 pathways, mitochondrial membrane potential and expression of genes were investigated. CP extract exhibited antiproliferative and cytotoxic effects on MDA MB-231 cells, what may be probably related to PI3K/Akt and ERK1/2 pathways. A decreased expression of apoptosis-related genes (TP53, CASP3, BAX and P21) was seen, whereas the expressions of BCL-2, BCL-XL, NOXA and PUMA were unaffected. CP extract induced mitochondrial dysfunction and LDH release, what indicated cell necrosis associated with reactive oxygen species production and decreased cell migration. Our findings provide a basis for future investigation of chemopreventive and/or therapeutic studies against apoptosis-resistant breast cancer, in animals and humans.