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.

The Study of Chemical Profile and Antioxidant Properties of Poplar-Type Polish Propolis Considering Local Flora Diversity in Relation to Antibacterial and Anticancer Activities in Human Breast Cancer Cells

“…The diversified results obtained may be due to more than 300 constituents of propolis samples (including benzoic acid, cinnamic acid, flavonoids) [ 62 ], which probably causes interactions between compounds of a synergistic, additive, or antagonistic nature. Inhibition of cancer cell migration by propolis extracts and individual components has been confirmed, among others, for glioblastoma, prostate, colorectal, lung, bladder, as well as breast cancer cells (MCF-7) [ 63 , 64 , 65 , 66 , 67 , 68 ].…”

Anticancer Activity of Propolis and Its Compounds

“…Extracts induce apoptosis by activating TP53, CASP3, BAX, p21 signaling and downregulating BCL2, BCL-XL, and PUMA. But in a similar study, researchers found that Brazilian propolis did not affect BCL-2, BCL-XL, NOXA, and PUMA expression [ 108 , 109 ].…”

Chemopreventive and Chemotherapeutic Effect of Propolis and Its Constituents: A Mini-review

“…Ethanolic extract of propolis and its active components (CAPE) are reported to exhibit antioxidant, cytotoxic, pro-apoptotic, autophagic, and anti-inflammatory activities in lipopolysaccharide stimulated MDA-MB-231 breast cancer cells by suppressing the TLR-4 signaling pathway [68][69][70]. Frión-Herrera and colleagues [71] demonstrated that treatment of breast cancer cells with propolis and its active ingredient (cardanol) triggered apoptosis (cytotoxicity) by modulation of PI3K/Akt, p38 MAPK, and ERK1/2 signaling pathways as well as by enhancing ROS generation and subsequent loss of mitochondrial potential. Propolis displays strong anti-proliferative and induces cell cycle arrest (G0/G1 and G2/M phase) by upregulating p21 and p27 expression [72].…”