High-throughput, Label-free Proteomics Identifies Salient Proteins and Genes in MDA-MB-231 Cells Treated with Natural Neem-based Electrochemotherapy.
Gowrisree VaradarajanJeya Shree ThulasidasPragatheiswar GiriIgnacio G CamarilloRaji SundararajanPublished in: Applied biochemistry and biotechnology (2022)
With the absence of the three most common receptor targets, and with high vascularity and higher-grade tumors, triple-negative breast cancer (TNBC) is the most aggressive of all breast cancer subtypes and is in need of additional/alternative/novel treatment strategies. With ~ 15% of the over 2 million new cases each year, there is an unmet need to treat TNBC. MDA-MB-231, human TNBC cells, were treated with neem leaf extract (Neem) and eight, 1200 V/cm, 100 µs electric pulses (EP), and their viability and proteomic profiles were studied. With EP + Neem, a lower viability of 37% was observed after 24 h, compared to 85% in the neem-only samples, indicating the efficacy of the combinational treatment. The proteomics results indicated significant upregulation of 525 proteins and downregulation of 572 proteins, with a number of different pathways in each case. These include a diverse group of proteins, such as receptors, heat shock proteins, and many others. The upregulated TCA cycle and OXPHOS pathways and the downregulated DNA replication and ubiquitin-mediated proteolytic pathways were associated with effective cell death, demonstrating the potency of this treatment. Viability results reveal the efficacious anticancer effects of the EP + Neem combination, via growth inhibition, on TNBC cells. Proteomics studies could readily identify the effected protein pathways, and their corresponding genes, that are responsible for cell death. This represents a potential therapeutic strategy against TNBC when patients are refractory to standard treatments.
Keyphrases
- cell cycle arrest
- cell death
- label free
- induced apoptosis
- genome wide
- mass spectrometry
- heat shock
- high throughput
- endothelial cells
- newly diagnosed
- oxidative stress
- endoplasmic reticulum stress
- breast cancer cells
- chronic kidney disease
- combination therapy
- small molecule
- prognostic factors
- dna methylation
- long non coding rna
- transcription factor
- genome wide identification
- binding protein
- heat stress
- heat shock protein
- amino acid
- pluripotent stem cells