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Quantitative Phosphoproteomics and Acetylomics of Safranal Anticancer Effects in Triple-Negative Breast Cancer Cells Publisher Pubmed



Ashrafian S1 ; Zarrineh M1, 4 ; Jensen P2 ; Nawrocki A2 ; Rezadoost H1 ; Ansari AM3 ; Farahmand L3 ; Ghassempour A1 ; Larsen MR2
Authors
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Authors Affiliations
  1. 1. Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, 1983963113, Iran
  2. 2. Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, DK-5230, Denmark
  3. 3. Integrative Oncology Department, Breast Cancer Research Center, Moatamed Cancer Institute, ACECR, Tehran, 1517964311, Iran
  4. 4. Department of Oncology and Pathology, Science for Life Laboratory, Karolinska Institutet, Solna, SE17165, Sweden

Source: Journal of Proteome Research Published:2022


Abstract

Safranal, as an aroma in saffron, is one of the cytotoxic compounds in saffron that causes cell death in triple-negative breast cancer cells. Our recent research reported the anti-cancer effects of safranal, which further demonstrated its impact on protein translation, mitochondrial dysfunction, and DNA fragmentation. To better understand the underlying mechanisms, we identified acetylated and phosphorylated peptides in safranal-treated cancer cells. We conducted a comprehensive phosphoproteomics and acetylomics analysis of safranal-treated MDA-MB-231 cells by using a combination of TMT labeling and enrichment methods including titanium dioxide and immunoprecipitation. We provide a wide range of phosphoproteome regulation in different signaling pathways that are disrupted by safranal treatment. Safranal influences the phosphorylation level on proteins involved in DNA replication and repair, translation, and EGFR activation/accumulation, which can lead the cells into apoptosis. Safranal causes DNA damage which is followed by the activation of cell cycle checkpoints for DNA repair. Over time, checkpoints and DNA repair are inhibited and cells are under a mitotic catastrophe. Moreover, safranal prevents repair by the hypo-acetylation of H4 and facilitates the transcription of proapoptotic genes by hyper-acetylation of H3, which push the cells to the brink of death. © 2022 American Chemical Society. All rights reserved.