Breast cancer (BC) is characterized by high disease heterogeneity and represents the most frequently diagnosed cancer among women worldwide. Complex and subtype-specific gene expression alterations participate in disease development and progression, with BC cells known to rewire their cellular metabolism to survive, proliferate, and invade. Hence, as an emerging cancer hallmark, metabolic reprogramming holds great promise for cancer diagnosis, prognosis, and treatment. Multi-omics approaches (the combined analysis of various types of omics data) offer opportunities to advance our understanding of the molecular changes underlying metabolic rewiring in complex diseases such as BC. Recent studies focusing on the combined analysis of genomics, epigenomics, transcriptomics, proteomics, and/or metabolomics in different BC subtypes have provided novel insights into the specificities of metabolic rewiring and the vulnerabilities that may guide therapeutic development and improve patient outcomes. This review summarizes the findings of multi-omics studies focused on the characterization of the specific metabolic phenotypes of BC and discusses how they may improve clinical BC diagnosis, subtyping, and treatment.
Background: Vepris dainelli (Rutaceae) is an endemic medicinal plant to Ethiopia, traditionally used for the treatment of abdominal cramp, intestinal worms, skin diseases and tooth pain. Methods: Roots and fruit extracts were subjected to silica gel column chromatographic separation to afford five alkaloids, reported for the first time from the species. The cytotoxic effects of alkaloids (2-4) were evaluated in vitro against the estrogen-responsive MCF-7 and estrogen-unresponsive MDA-MB-231 human breast cancer cell lines by MTS assay. Result: The results revealed that alkaloids (2-4) induced a significant reduction in cell growth of both breast cancer cell lines in a dose-dependent manner. Evodiamine (4) showed the highest potency against the aggressive metastatic MDA-MB-231 cell line at low micromolar concentrations. In addition, it highly arrested the cells in the G2/M phase, especially the MCF-7 cell line. By contrast, evoxanthine (2) and arborinine (3) exhibited higher cytotoxicity against MCF-7 than MDA-MB-231, and showed influencing the cell cycle in both cell lines by arresting some cells in the G2/M phase, preventing cells with damaged DNA from entering mitosis. Molecular docking analysis showed that all alkaloids inhibit human topoisomerase II α, compared with vosaroxin anti-cancer agent under clinical trial. The ADMET studies showed the alkaloids' highest drug-likeness properties, suggesting these alkaloids act as a drug and exhibit remarkable biological activities, except (5). DFT calculations indicated that studied alkaloids showed the lowest gap energy and were chemically reactive. Conclusion: We found that the results obtained from molecular docking, drug-likeness properties, ADMET analysis and DFT calculation are in good agreement with experimental studies. Hence, evoxanthine (2), arborinine (3), and evodiamine (4) may serve as a lead molecule that could be developed into potent topoisomerase II α inhibitors against human breast cancer cells.
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