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

Abstract

Dark sweet cherries (DSCs) are rich source of phenolics known to exert anticancer and anti-invasive activities. This study elucidated the molecular mechanisms underlying the activity of DSC phenolics against MDA-MB-453 breast cancer cells In Vitro. Cells were treated with DSC phenolics in whole extract (WE), and fractions enriched in anthocyanins (ACN) and proanthocyanidins (PCN) at concentrations that inhibited cell growth by 50%. Results showed that DSC phenolics suppressed Akt and PLCγ-1 activation, and inhibited cell motility and invasion, but only ACN reached significance. The extrinsic and intrinsic apoptotic pathways were also activated by DSC phenolics via caspase-8 cleavage and increased Bax/Bcl-2 ratio, with ACN exhibiting significant activation and stronger PARP-1 cleavage. Furthermore, sustained activation of mitogen-activated protein kinases (MAPKs) ERK1/2 and p38 was observed wherein ERK1/2 (U0126) and p38 (SB203580) inhibitors confirmed crosstalk ERK1/2-Akt and MAPK intrinsic mitochondrial pathways. In conclusion, DSC phenolics inhibited MDA-MB-453 breast cancer cells by targeting cell signaling pathways that induce apoptosis and suppress cell invasion, with ACN showing enhanced chemopreventive activities.

Acknowledgments

Authors thank the Office of International Linkages, University of the Philippines for providing Marjorie Anne A. Layosa the scholarship and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for providing Nara N. Lage the PDSE scholarship/process number 88881.132176/2016-01.

Disclosure Statement

The authors report no conflict of interest.

Author Contributions

MAL performed the experiments, analyzed data, prepared figures, and wrote the paper; NL performed the experiments and analyzed the data; BC contributed reagents and materials, and reviewed drafts of the paper; LA analyzed the data and reviewed drafts of the paper; SMT contributed reagents, materials, and analysis tools, and reviewed drafts of the paper; ST analyzed the data, contributed reagents, materials and analysis tools, and reviewed drafts of the paper; GN conceived and designed the experiments, performed the experiments, analyzed the data, contributed reagents, materials and analysis tools, wrote the paper, and reviewed drafts of the paper. All authors read and approved the final manuscript.

Additional information

Funding

This work was supported by the Northwest Cherry Growers.