High-throughput, Label-Free Quantitative Proteomic Studies of the Anticancer Effects of Electrical Pulses with Turmeric Silver Nanoparticles: an in vitro Model Study

Abstract

Triple negative breast cancer (TNBC) represents 15-20% of the over one million new breast cancer cases occurring each year. TNBC is an aggressive cancer phenotype, with low 5-year survival rates, high 3-year recurrence rates, and increased risk of metastasis. A lack of three commonly exploited hormone receptors renders tnBc resistant to endocrine therapies and lends to its critical absence of viable therapeutic targets. This necessitates the development of alternate and effective novel therapeutic strategies for tnBc. towards this, our current work seeks to develop the technique of electrical pulse (ep)-mediated turmeric silver nanoparticles (turnp) therapy, known as electrochemotherapy (ect), to effectively target TNBC cells. This technique involves the efficient delivery of natural bioactive molecules with anti-cancer effects via a biophysical means. In these experiments, the bioactive molecules are turmeric, a dried rhizome of Curcuma longa that has been used for centuries, both as a dietary supplement and as a medicine in Ayurveda (science of life) in the indian subcontinent and in traditional Chinese medicine. Our results reveal the combined effect of TurNP + ep treatment in reducing MDA-MB-231 cell viability to as low as 9% at 12 h. Showing biological selectivity, this combination treatment has a substantially lower effect on non-tumorigenic mammary epithelial MCF10A cells (67% viability). To gain mechanistic insights into the actions of TurNP-based ECT treatment, we performed high-throughput, label-free quantitative proteomics studies. proteomics results indicate that turnp + EP treatment significantly influenced expression of a diverse list of proteins, including receptors, transcription factors, structural proteins, kinases, and metabolic enzymes. This include the downregulation of 25 proteins in PI3K-Akt signaling pathway (such as GRB2, EGFR, EPHA2, GNB1, GNB2, 14-3-3 family, and Integrin family proteins), and 12 proteins (AKR1A1,

<p>Resistance and Overcoming Resistance in Breast Cancer</p>

“…129,130 A recent study demonstrated the anticancer effects of ECT against the MDA-MB-231 cell line, which is representative of the TNBC subtype. 131 These effects include the suppression of key proteins involved in the proliferation, differentiation, migration, survival, and apoptosis of cancer cells.…”

Recent advances of transcriptomics and proteomics in triple‐negative breast cancer prognosis assessment

“…G3BP (also known as 90‐kDa Mac‐2‐binding protein), which was before unreported associated with TNBC, is a member of the beta‐galactoside‐binding protein family. Additionally, another study also identified ENO1 as a potential biomarker of TNBC 100 …”

Clinical Applications and Immunological Aspects of Electroporation-Based Therapies

“…Such permeabilization is characterized by the uptake of external nonpermeant molecules in the cell cytoplasm and leakage of internal substances from the electropermeabilized cells [ 4 , 5 , 6 ]. Since then, this technique has being used and developed in several areas of biotechnology and medical research, such as bacterial transformation [ 7 , 8 ], cell electrofusion [ 9 , 10 ] transdermal drug delivery [ 11 , 12 ], CRISPR editing [ 13 ], CAR-T cell generation [ 14 ], DNA vaccines, including for the novel Sars-CoV-2 coronavirus [ 15 , 16 , 17 ], gene therapy [ 18 , 19 , 20 , 21 ], cancer treatment [ 22 , 23 , 24 ] and even in food processing [ 25 , 26 ] and environmental sanitation [ 27 , 28 ].…”