Browsing by Author "Lobos-Gonzalez, Lorena"

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    Annona cherimola Seed Extracts Trigger an Early Apoptosis Response and Selective Anticlonogenic Activity against the Human Gastric Carcinoma Cell Line SNU-1
    (2023) Macuer-Guzman, Johan; Giovagnoli-Vicuna, Claudia; Bernal, Giuliano; Lobos-Gonzalez, Lorena; de la Fuente-ortega, Erwin; Araya-Castillo, Michael; Ibanez, Cristian
    The aim of this study was to evaluate, for the first time, the antiproliferative, apoptotic and diminishing effects of the anchored growth-independent capacity of an ethanol macerate extract from the Annona cherimola seed (EMCHS) in the human gastric cancer cell line SNU-1. The cells treated with EMCHS (20 mu g/mL) significantly reduced the capacity to form clones of the tumor cell. Moreover, 50 mu g/mL of EMCHS extract induced apoptosis, as was shown by the Annexin-V assay. UHPLC-MS/MS analysis detected two acetogenins (Annonacinone and Annonacin) in the EMCHS, which could be largely responsible for its selective antiproliferative effect. The identification of fatty acids by GC-FID showed the presence of eight fatty acids, among which was, oleic acid, which has recognized activity as an adjuvant in antitumor treatments. Taken together, our results indicate that the EMCHS seems promising for use as a natural therapy against gastric cancer disease.
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    Increase in ADAR1p110 activates the canonical Wnt signaling pathway associated with aggressive phenotype in triple negative breast cancer cells
    (2022) Morales, Fernanda; Perez, Paola; Tapia, Julio C.; Lobos-Gonzalez, Lorena; Manuel Herranz, Jose; Guevara, Francisca; Rojas de Santiago, Pamela; Palacios, Esteban; Andaur, Rodrigo; Sagredo, Eduardo A.; Marcelain, Katherine; Armisen, Ricardo
    Triple-negative breast cancer (TNBC) represents a challenge in the search for new therapeutic targets. TNBCs are aggressive and generate resistance to chemotherapy. Tumors of TNBC patients with poor prognosis present a high level of adenosine deaminase acting on RNA1 (ADAR1). We explore the connection of ADAR1 with the canonical Wnt signaling pathway and the effect of modulation of its expression in TNBC. Expression data from cell line sequencing (DepMap) and TCGA samples were downloaded and analyzed. We lentivirally generated an MDA-MB-231 breast cancer cell line that overexpress (OE) ADAR1p110 or an ADAR knockdown. Abundance of different proteins related to Wnt/beta-catenin pathway and activity of nuclear beta-catenin were analyzed by Western blot and luciferase TOP/FOP reporter assay, respectively. Cell invasion was analyzed by matrigel assay. In mice, we study the behavior of tumors generated from ADAR1p110 (OE) cells and tumor vascularization immunostaining were analyzed. ADAR1 connects to the canonical Wnt pathway in TNBC. ADAR1p110 overexpression decreased GSK-3 beta, while increasing active beta-catenin. It also increased the activity of nuclear beta-catenin and increased its target levels. ADAR1 knockdown has the opposite effect. MDA-MB-231 ADAR1 (OE) cells showed increased capacity of invasion. Subsequently, we observed that tumors derived from ADAR1p110 (OE) cells showed increased invasion towards the epithelium, and increased levels of Survivin and CD-31 expressed in vascular endothelial cells. These results indicate that ADAR1 overexpression alters the expression of some key components of the canonical Wnt pathway, favoring invasion and neovascularization, possibly through activation of the beta-catenin, which suggests an unknown role of ADAR1p110 in aggressiveness of TNBC tumors.
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    Inhibition of PORCN Blocks Wnt Signaling to Attenuate Progression of Oral Carcinogenesis
    (2024) Pena-Oyarzun, Daniel; Flores, Tania; Torres, Vicente A.; Quest, Andrew F. G.; Lobos-Gonzalez, Lorena; Kretschmar, Catalina; Contreras, Pamela; Maturana-Ramirez, Andrea; Criollo, Alfredo; Reyes, Montserrat
    Purpose: Oral squamous cell carcinoma (OSCC) is commonly preceded by potentially malignant lesions, referred to as oral dysplasia. We recently reported that oral dysplasia is associated with aberrant activation of the Wnt/beta-catenin pathway, due to overexpression of Wnt ligands in a Porcupine (PORCN)-dependent manner. Pharmacologic inhibition of PORCN precludes Wnt secretion and has been proposed as a potential therapeutic approach to treat established cancers. Nevertheless, there are no studies that explore the effects of PORCN inhibition at the different stages of oral carcinogenesis.
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    Kinin Receptors B1 and B2 Mediate Breast Cancer Cell Migration and Invasion by Activating the FAK-Src Axis
    (2024) Gonzalez-Turen, Felipe; Lobos-Gonzalez, Lorena; Riquelme-Herrera, Alexander; Ibacache, Andres; Meza Ulloa, Luis; Droguett, Alexandra; Alveal, Camila; Carrillo, Bastian; Gutierrez, Javiera; Ehrenfeld, Pamela; Cardenas-Oyarzo, Areli
    Kinin receptors B1 and B2 are involved in migration and invasion in gastric, glioma, and cervical cancer cells, among others. However, the role of kinin receptors in breast cancer cells has been poorly studied. We aimed to reveal the impact of B1 and B2 receptors on migration and invasion in breast cancer cells and demonstrate their capacity to modulate in vivo tumor growth. MDA-MB-231, MCF-7, and T47D cells treated with Lys-des[Arg9]bradykinin (LDBK) or bradykinin (BK) were used to evaluate migration and invasion. Des-[Arg9]-Leu8-BK and HOE-140 were used as antagonists for the B1 and B2 receptors. MDA-MB-231 cells incubated or not with antagonists were subcutaneously inoculated in BALBc NOD/SCID mice to evaluate tumor growth. LDBK and BK treatment significantly increased migration and invasion in breast cancer cells, effects that were negated when antagonists were used. The use of antagonists in vivo inhibited tumor growth. Moreover, the migration and invasion induced by kinins in breast cancer cells were inhibited when focal adhesion kinase (FAK) and Src inhibitors were used. The novelty revealed in our work is that B1 and B2 receptors activated by LDBK and BK induce migration and invasion in breast cancer cells via a mechanism that involves the FAK-Src signaling pathway, and the antagonism of both receptors in vivo impairs breast tumor growth.
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    Peptide Targeted Gold Nanoplatform Carrying miR-145 Induces Antitumoral Effects in Ovarian Cancer Cells
    (2022) Salas-Huenuleo, Edison; Hernandez, Andrea; Lobos-Gonzalez, Lorena; Polakovicova, Iva; Morales-Zavala, Francisco; Araya, Eyleen; Celis, Freddy; Romero, Carmen; Kogan, Marcelo J.
    One of the recent attractive therapeutic approaches for cancer treatment is restoring downregulated microRNAs. They play an essential muti-regulatory role in cellular processes such as proliferation, differentiation, survival, apoptosis, cell cycle, angiogenesis, and metastasis, among others. In this study, a gold nanoplatform (GNPF) carrying miR-145, a downregulated microRNA in many cancer types, including epithelial ovarian cancer, was designed and synthesized. For targeting purposes, the GNPF was functionalized with the FSH33 peptide, which provided selectivity for ovarian cancer, and loaded with the miR-145 to obtain the nanosystem GNPF-miR-145. The GNPF-mir-145 was selectively incorporated in A2780 and SKOV3 cells and significantly inhibited cell viability and migration and exhibited proliferative and anchor-independent growth capacities. Moreover, it diminished VEGF release and reduced the spheroid size of ovarian cancer through the damage of cell membranes, thus decreasing cell viability and possibly activating apoptosis. These results provide important advances in developing miR-based therapies using nanoparticles as selective vectors and provide approaches for in vivo evaluation.