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    Preparation and characterization of PBS (polybutylene succinate) nanoparticles containing cannabidiol (CBD) for anticancer application
    (Elsevier, 2024) Freire, Natalia Freitas; Cordani, Marco; Aparicio-Blanco, Juan; Sanchez, Ana Isabel Fraguas; Dutra, Luciana; Pinto, Martina C. C.; Zarrabi, Ali; Pinto, Jose Carlos; Velasco, Guillermo; Fialho, Rosana
    Cannabidiol (CBD), a major constituent of Cannabis sativa, has demonstrated a broad range of therapeutic properties in human studies. Notably, CBD has shown anticancer activity in preclinical cancer models. However, its low water solubility poses challenges for bioavailability, necessitating the development of drug delivery systems to enhance its efficacy. This study aimed to create CBD-loaded Poly (butylene succinate) (PBS) nanoparticles and evaluate their effectiveness in in vitro cancer models. The nanoparticles, with an average size of 175 nm, were produced using a modified double emulsion/solvent evaporation technique. The release profile of CBD from the nanoparticles exhibited an initial rapid release followed by a slower sustained release. Cytotoxicity assays demonstrated that the CBD-PBS nanoparticles retained the anticancer effects of free CBD, selectively reducing the viability of cancer cell lines without affecting non -transformed fibroblasts. Additionally, the nanoformulation modulated key cellular pathways, as indicated by decreased AKT phosphorylation and increased LC3-II levels, suggesting that the encapsulated CBD preserved its ability to induce autophagy-mediated cell death in cancer cells. The nanoformulation also effectively inhibited cell migration in highly invasive prostate cancer cells, mirroring the effects of free CBD, while not impacting the migration of non -tumoral fibroblasts. These results underscore the therapeutic potential of this CBD nanoformulation, setting the stage for further in vivo investigations.
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    Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies
    (Bmc, 2024) Ambrosini, Giulia; Cordani, Marco; Zarrabi, Ali; Alcon-Rodriguez, Sergio; Sainz, Rosa M.; Velasco, Guillermo; Gonzalez-Menendez, Pedro
    Prostate cancer, as one of the most prevalent malignancies in males, exhibits an approximate 5-year survival rate of 95% in advanced stages. A myriad of molecular events and mutations, including the accumulation of oncometabolites, underpin the genesis and progression of this cancer type. Despite growing research demonstrating the pivotal role of oncometabolites in supporting various cancers, including prostate cancer, the root causes of their accumulation, especially in the absence of enzymatic mutations, remain elusive. Consequently, identifying a tangible therapeutic target poses a formidable challenge. In this review, we aim to delve deeper into the implications of oncometabolite accumulation in prostate cancer. We center our focus on the consequential epigenetic alterations and impacts on cancer stem cells, with the ultimate goal of outlining novel therapeutic strategies.