Electroporation enhances cell death in 3D scaffold-based MDA-MB-231 cells treated with metformin.

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer lacks estrogen, progesterone, and HER2 receptors and hence, is therapeutically challenging. Towards this, we studied an alternate therapy by repurposing metformin (FDA-approved type-2 diabetic drug with anticancer properties) in a 3D-scaffold culture, with electrical pulses. 3D cell culture was used to simulate the tumor microenvironment more closely and MDA-MB-231, human TNBC cells, treated with both 5 mM metformin (Met) and 8 electrical pulses at 2500 V/cm, 10 µs (EP1) and 800 V/cm, 100 µs (EP2) at 1 Hz were studied in 3D and 2D.

Efficacy of metformin and electrical pulses in breast cancer MDA-MB-231 cells.

Aim: Triple-negative breast cancer (TNBC) is a very aggressive subset of breast cancer, with limited treatment options, due to the lack of three commonly targeted receptors, which merits the need for novel treatments for TNBC. Towards this need, the use of metformin (Met), the most widely used type-2 diabetes drug worldwide, was explored as a repurposed anticancer agent. Cancer being a metabolic disease, the modulation of two crucial metabolites, glucose, and reactive oxygen species (ROS), is studied in MDA-MB-231 TNBC cells, using Met in the presence of electrical pulses (EP) to enhance the drug efficacy.

Efficacy of electrical pulse mediated tomato lipophilic extract on human breast cancer cell.

Aim: The purpose of this research is to study the effect of electrical pulse mediated tomato lipophilic extract (TLE) on human breast cancer MCF-7 and non-tumorigenic MCF-10A cells.

Materials And Methods: MCF-7 and MCF-10A cells were treated with 50 μg/mL TLE and eight 100 μs electric pulses of different electric field intensities (800, 1000, and 1200 V/cm), and the viability was studied using real time MT assay at 24 h of treatment. In addition, we studied cell viability of both the cells at 0 h using trypan blue assay and the ability to form colonies of both cells using colony forming unit (CFU) assay for all the treatments.

Enhancement of reactive oxygen species production in triple negative breast cancer cells treated with electric pulses and resveratrol.

Aim: Triple negative breast cancer (TNBC) is difficult to treat since it lacks all the three most commonly targeted hormone receptors. Patients afflicted with TNBC are treated with platinum core chemotherapeutics, such as cisplatin. Despite the initial effective anticancer effects of cisplatin, TNBC attenuates its effect and develops resistance eventually, which results in tumor reoccurrence.

High-throughput, Label-free Proteomics Identifies Salient Proteins and Genes in MDA-MB-231 Cells Treated with Natural Neem-based Electrochemotherapy.

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.

Enhanced Antiproliferation Potency of Electrical Pulse-Mediated Metformin and Cisplatin Combination Therapy on MDA-MB-231 Cells.

We investigated the combined potency of metformin and cisplatin on the MDA-MB-231, triple-negative breast cancer (TNBC) cells with the application of electrical pulses. There are no targeted therapies for this subset of breast cancer because of the absence of specific biomarkers. Cytotoxic chemotherapy is the mainstream mode of treatment for TNBC, and cisplatin is the most commonly used chemotherapeutic drug.

Cisplatin-based Electrochemotherapy Significantly Downregulates Key Heat Shock Proteins in MDA-MB-231-Human Triple-Negative Breast Cancer Cells.

Heat shock proteins (HSPs) are available and/or induced for the survival of all organisms, including eukaryotic, prokaryotic, and plants, from higher temperature stresses. They are the chaperone proteins that protect all cells against heat, as the name implies. In addition to thermal stress, they also protect them from chemical, physical, and other stresses, including exposure to oxidative stress, nutritional deficiencies, ultraviolet radiation, ethanol, viral infection, ischemia-reperfusion injury, and cancer-related stresses.

Electrochemotherapy Modulates Mammary Tumor Growth in Rats on a Western Diet Supplemented with Curcumin.

In the US, every 12 min, six women are diagnosed with breast cancer and one dies. This highlights a critical need for developing alternate therapies using natural compounds, which are cost effective and with less side effects. Curcumin, the yellow pigment of turmeric has been found to suppress initiation, progression, and metastasis of a variety of tumors.

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

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.

Author Correction: Quantitative proteomic analysis of enhanced cellular effects of electrochemotherapy with Cisplatin in triple-negative breast cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Quantitative proteomic analysis of enhanced cellular effects of electrochemotherapy with Cisplatin in triple-negative breast cancer cells.

Due to the lack of the three main receptors, triple negative breast cancer (TNBC) is refractive to standard chemotherapy. Hence, alternate therapies are needed. TNBCs utilize glycolysis, which heightens their growth, proliferation, invasiveness, chemotherapeutic resistance and poor therapeutic response.

Effective electrochemotherapy with curcumin in MDA-MB-231-human, triple negative breast cancer cells: A global proteomics study.

Curcumin (Cur), the yellow pigment of well-known turmeric (Curcuma longa L.) is effective in multiple cancers including triple negative breast cancer (TNBC). In combination with electrical pulses (EP), enhanced effects of curcumin (Cur + EP) are observed in TNBC cells.

Elevated leptin disrupts epithelial polarity and promotes premalignant alterations in the mammary gland.

Obesity is a highly prevalent and modifiable breast cancer risk factor. While the role of obesity in fueling breast cancer progression is well established, the mechanisms linking obesity to breast cancer initiation are poorly understood. A hallmark of breast cancer initiation is the disruption of apical polarity in mammary glands.

Proteomic Analysis Reveals That an Extract of the Plant Lippia origanoides Suppresses Mitochondrial Metabolism in Triple-Negative Breast Cancer Cells.

Triple-negative breast cancer is an aggressive subtype of breast cancer with low 5-year survival rates, high 3-year recurrence rates, and no known therapeutic targets. Recent studies have indicated that triple-negative breast cancers possess an altered metabolic state with higher rates of glycolysis, mitochondrial oxidative phosphorylation, and increased generation and utilization of tricarboxylic acid cycle intermediates. Here, we utilized label-free quantitative proteomics to gain insight into the anticancer mechanisms of a methanolic extract from the Central American plant Lippia origanoides on MDA-MB-231 triple-negative breast cancer cells.

Lippia origanoides extract induces cell cycle arrest and apoptosis and suppresses NF-κB signaling in triple-negative breast cancer cells.

Treatments targeting hormone receptors typically fail to provide a positive clinical outcome against triple-negative breast cancers (TNBC), which lack expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2/neu). Towards identifying viable treatments for aggressive breast cancer, we have tested an extract of the tropical plant Lippia origanoides (LOE) on TNBC and normal cells lines to uncover its potential anticancer effects. Treatment with LOE reduced TNBC cell viability in a dose-dependent manner to a greater extent than in normal mammary epithelial MCF10A cells.

Ultra-microsecond pulsed curcumin for effective treatment of triple negative breast cancers.

Triple negative breast cancer (TNBC) is difficult to treat due to lack of the three receptors, commonly used for treating breast cancers. Current standard of cure is either ineffective or refractive to many patients. Thus, there is a critical need for alternate, affordable therapies for TNBC cancers.

Stilbenoids remodel the DNA methylation patterns in breast cancer cells and inhibit oncogenic NOTCH signaling through epigenetic regulation of MAML2 transcriptional activity.

DNA hypomethylation was previously implicated in cancer progression and metastasis. The purpose of this study was to examine whether stilbenoids, resveratrol and pterostilbene thought to exert anticancer effects, target genes with oncogenic function for de novo methylation and silencing, leading to inactivation of related signaling pathways. Following Illumina 450K, genome-wide DNA methylation analysis reveals that stilbenoids alter DNA methylation patterns in breast cancer cells.

Leptin-STAT3-G9a Signaling Promotes Obesity-Mediated Breast Cancer Progression.

Obesity has been linked to breast cancer progression but the underlying mechanisms remain obscure. Here we report how leptin, an obesity-associated adipokine, regulates a transcriptional pathway to silence a genetic program of epithelial homeostasis in breast cancer stem-like cells (CSC) that promotes malignant progression. Using genome-wide ChIP-seq and RNA expression profiling, we defined a role for activated STAT3 and G9a histone methyltransferase in epigenetic silencing of miR-200c, which promotes the formation of breast CSCs defined by elevated cell surface levels of the leptin receptor (OBR(hi)).

Maternal exercise during pregnancy reduces risk of mammary tumorigenesis in rat offspring.

Breast cancer is the most common cancer among women. Emerging research indicates that modifying lifestyle factors during pregnancy may convey long-term health benefits to offspring. This study was designed to determine whether maternal exercise during pregnancy leads to reduced mammary tumorigenesis in female offspring.

Characterization of synergistic anti-cancer effects of docosahexaenoic acid and curcumin on DMBA-induced mammary tumorigenesis in mice.

Background: The major obstacles to the successful use of individual nutritional compounds as preventive or therapeutic agents are their efficacy and bioavailability. One approach to overcoming this problem is to use combinations of nutrients to induce synergistic effects. The objective of this research was to investigate the synergistic effects of two dietary components: docosahexaenoic acid (DHA), an omega-3 fatty acid present in cold-water fish, and curcumin (CCM), an herbal nutrient present in turmeric, in an in vivo model of DMBA-induced mammary tumorigenesis in mice.

Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression.

Obesity is a recently established risk factor for breast cancer incidence and mortality. A characteristic of obesity is elevated circulating levels of adipocyte-derived hormone leptin. Evidence indicates that leptin plays an important role in mammary tumor formation; however, the mechanisms involved are poorly understood.

Identification of proteins secreted from leptin stimulated MCF-7 breast cancer cells: a dual proteomic approach.

Leptin is an adipocyte-derived hormone that regulates energy expenditure and food intake. A significant role for leptin in breast cancer has also been indicated by the resistance of leptin knockout mice in development of mammary tumors. In vitro, leptin induces proliferation of MCF-7 cells by activating cellular signaling pathways (1, 11, 12, 16, 17, 56).

Nonlinear optical imaging to evaluate the impact of obesity on mammary gland and tumor stroma.

Obesity is an established risk factor for breast cancer incidence and mortality. However, the mechanism that links obesity to tumorigenesis is not well understood. Here we combined nonlinear optical imaging technologies with an early-onset diet-induced obesity breast cancer animal model to evaluate the impact of obesity on the composition of mammary gland and tumor stroma.