Integrative analysis of metabolic subtypes in triple-negative breast cancer reveals new therapeutic strategies

Gong, Yue; Ji, Peng; Xiao, Yaoxing; Ma, Ding; Jin, Ming‐Liang; Hu, Xin; Jiang, Yi; Shao, Zhimin

doi:10.1093/annonc/mdz416.002

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“…Other major changes in protein expression due to TurNP + EP treatment were also observed for proteins involved in glycolysis, TCA cycle and OXPHOS. Majority of key glycolytic enzymes were downregulated in agreement with previous reports [44][45][46][47][48][49][50][51][52][53] . For example, ENO1 is a highly expressed TNBC biomarker and its function is positively related with the distinct TNBC metabolism 44,45 .…”

Section: Discussionsupporting

confidence: 92%

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

Mittal

Camarillo

Varadarajan

et al. 2020

Sci Rep

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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,

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Section: Discussionsupporting

confidence: 92%

“…treatment because these enzymes are known to overexpress in various cancers [51][52][53] . These results were validated by demonstrating a good correlation between mRNA and protein level expressions of LDHB and ENO1 for the different treatments.…”

Section: Discussionmentioning

confidence: 99%