Dark Sweet Cherry (Prunus avium) Phenolics Enriched in Anthocyanins Induced Apoptosis in MDA-MB-453 Breast Cancer Cells through MAPK-Dependent Signaling and Reduced Invasion via Akt and PLCγ-1 Downregulation

Sweet Cherries as Anti-Cancer Agents: From Bioactive Compounds to Function

“…These properties are uniquely determined by the extract’s chemical composition ( Table 1 ) and its enrichment in specific bioactive components, which, as discussed in Section 3 , depends on several factors, namely the cultivar place and harvest time [ 19 , 24 , 40 ]. In vitro and in vivo studies demonstrated that polyphenols are the main responsible for the anti-proliferative and pro-apoptotic effects among the sweet cherries’ bioactive compounds [ 18 , 19 , 24 , 40 , 45 , 77 , 78 , 79 , 80 , 81 ]. Sweet cherry extracts rich in polyphenols inhibited the viability of human prostate non-neoplastic PNT1A cells, and human lung A549, cervix HeLa, brain SK-B-NE (2)-C, SH-SY5Y and prostate cancer LNCaP cells in a concentration-dependent manner [ 19 , 45 ].…”

“…Experiments using three different types of extracts, whole sweet cherry extract or extracts enriched in anthocyanins or proanthocyanins, showed that all decreased AKT mRNA levels [ 79 ]. However, only anthocyanins-enriched extract decreased the levels of the active phosphorylated AKT (p-AKT, Figure 2 ) [ 80 ]. The downstream targets of PI3K/AKT signaling were also modulated by the sweet cherry extract.…”

“…The activity of sweet cherry extract was also shown to influence the p38-mitogen-activated protein kinase (p38-MAPK) signaling pathway ( Figure 2 ). In MDA-MD-453 cells, sweet cherry extract increased the p-p-38-MAPK/p38-MAPK protein ratio and enhanced the expression levels of the extracellular signal-regulated kinase (ERK) 1/2, and c-Jun N-terminal kinase (JNK) phosphorylated forms [ 80 ]. However, the p-ERK1/2/full ERK1/2 ratio was not altered.…”

“…However, the p-ERK1/2/full ERK1/2 ratio was not altered. Nevertheless, treatment with U0126, an inhibitor of the ERK1/2 signaling pathway, abrogated the downregulation of p-AKT induced by the sweet cherry extract enriched in anthocyanins [ 80 ]. This finding is quite interesting because it demonstrates that the effect of sweet cherry extract negatively regulating the PI3K/AKT pathway can be modulated by the ERK1/2 pathway.…”

“…Studies concerning the effect of sweet cherry extracts in apoptosis are scarce, being limited to human breast and prostate cells [ 45 , 79 , 80 ]. Sweet cherry extracts induced apoptosis in the breast cancer MDA-MB-453 cell model by controlling the expression and activity of cell survival regulators and signaling pathways [ 79 , 80 ]. Similarly to what was described for cell proliferation, the effect of sweet cherry extracts on apoptosis targeted the PI3K/AKT and MAPK/p38-MAPK/JNK pathways, with the activation of the intrinsic and extrinsic pathways of apoptosis ( Figure 2 ).…”