2024-03-29T07:14:06Zhttps://riubu.ubu.es/oai/requestoai: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/
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RIUBU. Repositorio Institucional de la Universidad de Burgos
http://hdl.handle.net/10259/7559