2026-04-29T13:03:39Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/75592023-04-18T12:48:15Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925

Antimetastatic Properties of Prodigiosin and the BH3-Mimetic Obatoclax (GX15-070) in Melanoma Espona Fiedler, Margarita Manuel Manresa, Pilar Benítez-García, Cristina Fontova Pale, Pere Quesada Pato, Roberto Soto Cerrato, Vanessa Pérez Tomás, Ricardo Metastasis Obatoclax Prodigiosin Prodiginines BH3-mimetic Melanoma Migration Química orgánica Salud Medicina Chemistry, Organic Health Medicine Metastasis is the primary cause of death in cancer patients. Many current chemotherapeutic agents only show cytotoxic, but not antimetastatic properties. This leads to a reduction in tumor size, but allows cancer cells to disseminate, which ultimately causes patient death. Therefore, novel anticancer compounds with both effects need to be developed. In this work, we analyze the antimetastatic properties of prodigiosin and obatoclax (GX15-070), anticancer drugs of the Prodiginines (PGs) family. We studied PGs’ effects on cellular adhesion and morphology in the human primary and metastatic melanoma cell lines, SK-MEL-28 and SK-MEL-5, and in the murine melanoma cell line, B16F10A. Cell adhesion sharply decreased in the treated cells, and this was accompanied by a reduction in filopodia protrusions and a significant decrease in the number of focal-adhesion structures. Moreover, cell migration was assessed through the wound-healing assay and cell motility was severely inhibited after 24 h of treatment. To elucidate the molecular mechanisms involved, changes in metastasis-related genes were analyzed through a gene-expression array. Key genes related to cellular invasion, migration and chemoresistance were significantly down-regulated. Finally, an in vivo model of melanoma-induced lung metastasis was established and significant differences in lung tumors were observed in the obatoclax-treated mice. Altogether, these results describe, in depth, PGs’ cellular antimetastatic effects and identify in vivo antimetastatic properties of Obatoclax. This research has been funded by Instituto de Salud Carlos III (Grants PI18/00441; FIS PI10/00338) (Co-funded by European Regional Development Fund. ERDF, a way to build Europe). 2023-03-20T08:26:03Z 2023-03-20T08:26:03Z 2022-12 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/10259/7559 10.3390/pharmaceutics15010097 1999-4923 eng Pharmaceutics. 2022, V. 15, n. 1, 97 https://doi.org/10.3390/pharmaceutics15010097 info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI18%2F00441/ES/EVALUACION TERAPEUTICA PRECLINICA EN CANCER DE PULMON DE INHIBIDORES DE SURVIVINA MEDIANTE LA UTILIZACION DE FORMULACIONES NANOENCAPSULADAS Y TERAPIAS COMBINADAS/ info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI10%2F00338/ES/ Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf MDPI