Decreased expression of p53 is associated with down expression of zyxin in breast cancer.

Background and Aims: Breast cancer (BC) is considered one of the most common malignant tumors leading to death in women, and genetic factors have a crucial role in BC pathogenesis. Zyxin (ZYX) is one of these factors that may be important in p53 level and function. Thus, the present work aimed to investigate the ZYX gene and protein expression in tumor tissue and matched margin tissue and its correlation with the p53 expression. Methods: In a present case-control study, 30 tumors and 30 matched margin tissues were obtained from Iran Tumor Bank/Tehran University of Medical Sciences. Real-time polymerase chain reaction and western blot analysis techniques were applied to evaluate the genes and protein expression, respectively. Results: The data showed that expression of the ZYX gene in tumor tissues significantly decreased (p = 0.0274) compared to matched margin tissues. In contrast, the p53 gene expression in tumor tissues had no significant difference with matched margin tissues. Additionally, we observed that ZYX and p53 genes expression in tumor tissues of estrogen receptor-positive patients had significant elevation than estrogen receptor-negative patients (p < 0.001, p < 0.001, respectively). The data of the western blot analysis technique showed that protein expression of ZYX (p = 0.0024) and P53 protein (p = 0.0218) in tumor tissues was significantly reduced compared to matched margin tissues. Additionally, our analysis showed a direct and significant correlation between the expression of ZYX and p53 proteins (r = 0.7797, p = 0.0126) and expression of ZYX and p53 genes (r = 0.3079, p = 0.0187). Conclusion: Based on our observation, ZYX might have a tumor suppressor role and is associated with p53.

A comparative study of sericin and gluten for magnetic nanoparticle-mediated drug delivery to breast cancer cell lines.

With breast cancer emerging as a pressing global health challenge, characterized by escalating incidence rates and geographical disparities, there is a critical need for innovative therapeutic strategies. This comprehensive research navigates the landscape of nanomedicine, specifically focusing on the potential of magnetic nanoparticles (MNPs), with magnetite (Fe3O4) taking center stage. MNPs, encapsulated in biocompatible polymers like silica known as magnetic silica nanoparticles (MSN), are augmented with phosphotungstate (PTA) for enhanced chemodynamic therapy (CDT). PTA is recognized for its dual role as a natural chelator and electron shuttle, expediting electron transfer from ferric (Fe3+) to ferrous (Fe2+) ions within nanoparticles. Additionally, protein-based charge-reversal nanocarriers like silk sericin and gluten are introduced to encapsulate (MSN-PTA) nanoparticles, offering a dynamic facet to drug delivery systems for potential revolutionization of breast cancer therapy. This study successfully formulates and characterizes protein-coated nanocapsules, specifically MSN-PTA-SER, and MSN-PTA-GLU, with optimal physicochemical attributes for drug delivery applications. The careful optimization of sericin and gluten concentrations results in finely tuned nanoparticles, showcasing uniform size, enhanced negative zeta potential, and remarkable stability. Various analyses, from Dynamic Light Scattering (DLS) and scanning electron microscopy (SEM) to transmission electron microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), X-Ray diffraction analysis (XRD), and Thermogravimetric analysis (TGA), provide insights into structural integrity and surface modifications. Vibrating Sample Magnetometer (VSM) analysis underscores superparamagnetic behavior, positioning these nanocapsules as promising candidates for targeted drug delivery. In vitro evaluations demonstrate dose-dependent inhibition of cell viability in MCF-7 and Zr-75-1 breast cancer cells, emphasizing the therapeutic potential of MSN-PTA-SER and MSN-PTA-GLU. The interplay of surface charge and pH-dependent cellular uptake highlights the robust stability and versatility of these nanocarriers in tumor microenvironment, paving the way for advancements in targeted drug delivery and personalized nanomedicine. This comparative analysis explores the suitability of silk sericin and gluten, unraveling a promising avenue for the development of advanced, targeted, and efficient breast cancer treatments.

Enhancing Cisplatin Efficacy with Low Toxicity in Solid Breast Cancer Cells Using pH-Charge-Reversal Sericin-Based Nanocarriers: Development, Characterization, and In Vitro Biological Assessment.

Platinum-based chemotherapeutic agents are widely employed in cancer treatment because of their effectiveness in targeting DNA. However, this indiscriminate action often affects both cancerous and normal cells, leading to severe side effects and highlighting the need for innovative approaches in achieving precise drug delivery. Nanotechnology presents a promising avenue for addressing these challenges. Protein-based nanocarriers exhibit promising capabilities in the realm of cancer drug delivery with silk sericin nanoparticles standing out as a leading contender. This investigation focuses on creating a sericin-based nanocarrier (SNC) featuring surface charge reversal designed to effectively transport cisplatin (Cispt-SNC) into MCF-7 breast cancer cells. Utilizing AutoDock4.2, our molecular docking analyses identified key amino acids and revealed distinctive conformational clusters, providing insights into the drug-protein interaction landscape and highlighting the potential of sericin as a carrier for controlled drug release. The careful optimization and fabrication of sericin as the carrier material were achieved through flash nanoprecipitation, a straightforward and reproducible method that is devoid of intricate equipment. The physicochemical properties of SNCs and Cispt-SNCs, particularly concerning size, surface charge, and morphology, were evaluated using dynamic light scattering (DLS) and scanning electron microscopy (SEM). Chemical and conformational analyses of the nanocarriers were conducted using Fourier-transform infrared spectroscopy (FTIR) and circular dichroism (CD), and elemental composition analysis was performed through energy-dispersive X-ray spectroscopy (EDX). This approach aimed to achieve the smallest nanoparticle size for Cispt-SNCs (180 nm) and high drug encapsulation efficiency (84%) at an optimal sericin concentration of 0.1% (w/v), maintaining a negative net charge at a physiological pH (7.4). Cellular uptake and cytotoxicity were investigated in MCF-7 breast cancer cells. SNCs demonstrated stability and exhibited a pH-dependent drug release behavior, aligning with the mildly acidic tumor microenvironment (pH 6.0-7.0). Efficient cellular uptake of Cispt-SNC, along with DNA fragmentation and chromatin condensation, was found at pH 6, leading to cell apoptosis. These results collectively indicate the potential of SNCs for achieving controlled drug release in a tumor-specific context. Our in vitro studies reveal the cytotoxicity of both cisplatin and Cispt-SNCs on MCF-7 cells. Cisplatin significantly reduced cell viability at 10 µM concentration (IC50), and the unique combination of sericin and cisplatin showcased enhanced cell viability compared to cisplatin alone, suggesting that controlled drug release is indicated by a gradient decrease in cell viability and highlighting SNCs as promising carriers. The study underscores the promise of protein-based nanocarriers in advancing targeted drug delivery for cancer therapy.